Monday, May 7, 2012

Encephalitis

Encephalitis is defined as a condition of irritation and swelling (inflammation) of the brain, as a result of virus, bacteria and others invasion.

Symptoms
Symptoms of Encephalitis are not limit to
1. Headache
In the study to evaluate 43 participants identified with earlier intracranial infection, whereof three had more than one infection: bacterial meningitis (n=19), lymphocytic meningitis (n=18), encephalitis (n=9), and brain abscess (n=1).The mean interval from infection to participation in HUNT 3 was 11.2 (range 1.5-19.7) years. There was no significant increase in the prevalence of headache (OR 1.10, 95% CI 0.58-2.07), its subtypes (migraine, or tension-type headache), or chronic daily headache (OR 1.85, 95% CI 0.45-7.68) amongst participants with previous intracranial infection compared with the surrounding population.(1)

2. Fever
West Nile virus (WNV), a member of the family Flaviviridae (genus Flavivirus), is a mosquito-borne virus first isolated in 1937 in the West Nile district of Uganda. According to the study of National Institute of Infectious Diseases, WN encephalitis was first reported in the Western Hemisphere in the summer of 1999, there was an outbreak in New York City. Epidemic WNV strains in North America are severely pathogenic, however, attenuated WNV strains were found in Texas and Mexico in 2003. The principal vectors of WNV transmission in North America are Culex. pipiens, Cx. Quinquefasciatus, Cx. restuans, Cx salinarius and Cx talsalis. The number of WN fever case has exceeded 27,000 since 1999 in the United States and 4,600 since 2002 in Canada. The first imported case of West Nile fever in Japan was confirmed in September, 2005(2).

3. Confusion
There is report that a seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. During the year before his admission he had experienced four spontaneously regressive episodes of feverish confusion. Exploration of these episodes disclosed a paraneoplastic limbic encephalitis due to an underlying Hodgkin's disease.(3)

4. Drowsiness
In the information collected on 5 previously healthy patients (2 boys and 3 girls, aged 10-15 years) with 2009 H1N1 influenza who presented with late onset (>3 days after fever) and long-standing (>48 hours) delirious behavior. Each exhibited mild to moderate drowsiness between the episodes of delirious behavior, in the report of Kameda Medical Center(4)

5. Fatigue
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is about 2 to 4 times more common in women than in men. It is associated with extreme and prolonged fatigue that isn't relieved by rest(5)

6. Others symptoms
In the study to investigate Lyme borreliosis, a multisystem disorder caused by Borrelia burgdorferi (Bb) and its effects conducted by Zagreb University Hospital Centre, Dr Markeljević J, and the team of scientist showed that neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection, other neurologic complications may occur, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panicc attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome. We describe here a patient with a triad of unusual symptoms in chronic LNB including tremor, seizures and psychosis. Standardized medical interview, neurologic examination, neuroimaging, serum and CSF serology as well as EEG and EMNG evaluation were performed(6).


7. Etc.

II. Causes and Risk Factors
A. Causes
1. Encephalitis caused by virus
a. Rabies virus 
Rabies virus is the etiological agent of an acute encephalitis, which in absence of post exposure treatment is fatal in almost all cases. In the study to analyze the role of the immuno-inhibitory molecule B7-H1 in this virus strategy, show that the B7-H1/PD-1 pathway can be exploited locally and in an organ specific manner--here the nervous system--by a neurotropic virus to promote successful host invasion(7).

b. Herpes simplex 
Herpes simplex encephalitis (HSE) is a life-threatening consequence of herpes simplex virus (HSV) infection of the central nervous system (CNS). Although HSE is rare, mortality rates reach 70% in the absence of therapy and only a minority of individuals return to normal function, according to Scientist at the University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center(8).

c. Poliovirus
Poliovirus virion RNA contains a single covalently bound sequence of polyadenylic acid which is approximately 49 nucleotides long. A single, slightly longer polyadenylic acid sequence is contained in Eastern Equine Encephalitis virus RNA(9).

d. Measles virus
There are report from The Hospital for Sick Children that a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease, as a brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscop(11).

e. JC virus
Scientist at the Karolinska Institute, Huddinge University Hospital showed that JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF) samples from patients with progressive multifocal leukoencephalopathy (PML) but not in CSF samples from patients with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis. This suggests that inflammatory processes in the brain do not necessarily reactivate JCV, which further supports the proposal that the presence of JCV DNA in the CSF is diagnostic for PML(12)

f.  Japanese encephalitis virus
Japanese encephalitis virus (JEV) has found to be a pathogen causing febrile syndrome, encephalitis, and death. Envelop (E) glycoprotein is the major target of inducing neutralizing antibodies and protective immunity in host(13)

g.  West Nile encephalitis virus
WNV disseminates to the central nervous system (CNS) and causes severe disease primarily in the immunocompromised and elderly. Experimental studies have made significant progress in dissecting the viral and host factors that determine the pathogenesis and outcome of WNV infection.(14).

h.  Eastern equine encephalitis virus (EEE virus)
The eastern equine encephalitis (EEE) complex consists of four distinct genetic lineages: one that circulates in North America (NA EEEV) and the Caribbean and three that circulate in Central and South America (SA EEEV). Differences in their geographic, pathogenic, and epidemiologic profiles prompted evaluation of their genetic diversity and evolutionary histories, according to University of Texas Medical Branch(15).

i. Etc.

2. Encephalitis caused by bacteria infection
a. Bacterial meningitis, such as herpes simplex virus
Health records from 2002 to 2006 of all children 6 months to 6 years with a discharge diagnosis from the Hospital for Sick Children (Toronto, ON) of febrile convulsion, meningitis, or encephalitis were reviewed. Rates of bacterial meningitis and HSV encephalitis in children presenting with complex febrile seizures were calculated(16). In the article of "Meningitis and Encephalitis: Introduction", the author(s) wrote "Inflammation of the meninges (meningitis) and inflammation of the brain (encephalitis) often are seen simultaneously (meningoencephalitis) in the same animal, although either can be seen separately. In animals with meningoencephalitis, the clinical signs of meningitis often precede the clinical signs of encephalitis and may remain the predominant feature of the illness"(17)

b.Syphilis
According to a report by centre hospitalier universitaire  17-year-old patient presented for one year progressive dementia, frontal syndrome and extra pyramidal syndrome. The cerebral CT scan showed a diffuse cortical and subcortical atrophy. Blood and CSF positive antibodies confirmed the diagnosis of late congenital meningoencephalitis due to syphilis(18)
 
3. Parasites and Others
a. Toxoplasmosis
Toxoplasmosis is a rare but rapidly fatal complication that can occur following hematopoietic stem cell transplantation (HSCT), according to Kyushu University Graduate School of Medical Sciences, in a study of over a 17-yr period at our institutions, two patients received a conventional conditioning regimen followed by transplantation from an HLA-matched donor; however, they developed severe graft-vs.-host disease, which required intensive immunosuppressive therapy. Despite prophylactic treatment with trimethoprim/sulfamethoxazole, their immunosuppressive state, as indicated by a low CD4(+) cell count, might have resulted in toxoplasmosis encephalitis.(19)
 
b. Malaria  
Malaria is a mosquito-borne infectious disease and associated Encephalitis to. In the article of "Mosquitoes and Diseas" posted in Illinois department of Public Health wrote "Today, however, the threat of developing encephalitis from mosquitoes is far greater than the threat of malaria in the United States. Encephalitis, meningitis and other diseases can develop from the bites of mosquitoes infected with certain viruses. These include the viruses of West Nile, St. Louis encephalitis, LaCrosse (California) encephalitis, and Eastern equine and Western equine encephalitis"(20)

c. Primary amoebic meningoencephalitis
Primary amoebic meningoencephalitis (PAM or PAME) is a disease of the central nervous system caused by infection from Naegleria fowleri. In the report of Dayanand Medical College and Hospital (DMC & H), a 36-year-old, Indian countryman who had a history of taking bath in the village pond. Computerized tomography (CT) scan of brain showed a soft tissue non-enhancing mass with erosion of sphenoid sinus. However CSF findings showed no fungal or bacterial pathogen. Trophozoites of Naegleria fowleri were detected in the direct microscopic examination of CSF and these were grown in culture on non-nutrient agar(21).

d. Lyme disease 
Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi (Bb). Neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection(22).

e. Cryptococcus neoformans 
 reported from the Ohgaki Municipal Hospital., a 46-year-old man with hepatoma was admitted with chief complaints of headache, fever and dizziness. On admission, cerebellar signs (disturbance of finger-to-nose test and of heel-to-knee test, intention tremor, and truncal ataxia) were neurologically noted.  Head CT showed swelling and enhancement of the cerebellar cortex and dilatation of the cerebral ventriculi. Cryptococcus neoformans was detected in a culture of the patient's CSF.(23)

f. Streptococci 
Encephalitis lethargica or von Economo disease is an atypical form of encephalitis. Also known as "sleepy sickness" (though different from the sleeping sickness transmitted by the tsetse fly)(24)

g. Staphylococci 
In the study in 1997, 4,409 cases of meningitis and 632 cases of encephalitis were reported in Poland. Meningitis incidence rate was 11.4 per 100,000, and was 3-times lower than in 1996. The etiology of meningitis cases was as follows: 2,713 (61.5%) were due to viral agents (ECHO 30 dominated), 1,351 (30.7%) were caused by bacterial agents: 144 meningococcal (3.3%) and 1,207 other bacterial. The bacterial etiology was following: 33.2% were due to Streptococcus pneumoniae, 27.6% were cased by Haemophilus influenzae type b, and 11.6% by Staphylococci.(25)

h. Autoimmune disease 
Autoimmune limbic encephalitis is a rare disorder, characterised by the subacute onset of seizures, short-term memory loss, and psychiatric and behavioural symptoms. Initially, it was recognised as a paraneoplastic disorder, but recently a subgroup of patients without systemic cancer was identified. This type of limbic encephalitis is associated with voltage-gated potassium channel (VGKC) or N-methyl-D-aspartate receptor (NMDAR) antibodies(26).

i. Etc.

B. Risk factors
a. Age(27)
Age and people with weakened immune system are susceptible to be infected by encephalitis and bacteria virus,  depending on the type of encephalitis virus.
a.1. Newborn and infants are particularly at risk for herpes virus and arboviruses,
a.2. Infants are most vulnerable to Western equine encephalitis. Older
a.3. Children and teenagers are vulnerable to Eastern equine and La Crosse encephalitis.
a.4. Older and elderly adults are at higher risk for Eastern equine, St. Louis, and West Nile encephalitis.

b. Weakened immune system.
People with HIV/AIDS, taking immune-suppressing drugs compromised or weakened immune system are at higher risk of encephalitis.

c. Geographic regions
People who live in the geographic region with Mosquito-borne or tick-borne viruses are at higher risk of encephalitis.

d. Outdoor activities.
People who are engage a lots of outdoor activities or work that expose to ticks or mosquitoes are at increased risk of encephalitis. 

e. Seasonal risk
Mosquitoes and ticks season

f. Etc.


III. Complications
1. Brain damage
Encephalitis can cause brain damage as a result of replication of viruses after entering brain of that depleting the energy and oxygen in the brain cell. In case of autoimmune encephalitis the immune system makes antibodies that cause damage to neurons or other brain cells as a result of the accumulateion of fluid, white blood cells, the contents of dead nerve cells and disabled viruses(28). Some resaerchers suggested that Glutamate is the major excitatory CNS neurotransmitter. Glutamate receptor autoantibodies have now been called to our attention, as they are found in many patients with epilepsy, systemic lupus erythematosus (SLE) and encephalitis, and can unquestionably cause brain damage(29).
Other found that The blood-brain barrier (BBB) serves to protect the central nervous system (CNS) from damage by exogenous molecules. Japanese encephalitis (JE), caused by a neurotropic flavivirus, leads to inflammation in the CNS, neuronal death and also compromises the structural and functional integrity of the BBB(30).

2. Stroke 
Stroke are associated with the complication of Encephalitis. In the study to investigate Herpes simplex virus type-1 encephalitis and occipital ischemic stroke, the team at Erasmus MC Sophia Children's Hospital said "Childhood ischemic stroke is a rare complication of herpes simplex virus type-1 encephalitis" in a description of healthy 3-year-old girl who presented with bilateral occipital ischemic stroke, attributable to herpes simplex virus type-1 encephalitis, highlighting the importance of viral diagnostics in cerebrospinal fluid"(31).

3. Seizures    
Scientists at the National Center of Neurology and Psychiatry have found that Acute encephalitis with refractory, repetitive partial seizures (AERRPS) represents a peculiar form of encephalitis mainly affecting children. They usually present abruptly with seizure or impaired consciousness as well as high-grade fever following antecedent infection(32)

4. Death 
Compared to other infectious diseases, encephalitis has a high mortality rate. Overall, approximately 10% of those with encephalitis die from the brain inflammation or complications such as secondary infection. Some forms of encephalitis have more severe courses, including herpes simplex virus encephalitis, in which mortality is up to 30% with treatment, and 70-80% without(33).

5. Etc.

IV. Diagnosis
A. Misdiagnosis
It is important to differentiate encephalitis correctly from other disorders that may cause similar neurological symptoms and which may have very different treatments, including include bacterial meningitis, stroke, brain tumours, drug reactions and metabolic disturbances. In a report on Encephalitis Global community study (a sad story) Mcgraw wrote " He (My son) went to an emergency room 4 times in 3 days. He had high white blood cell counts, was complaining of chest pain, arm numbness and a general feeling of feeling very very ill. His first diagnosis was Rhabdamyolisis and (you guessed it) sinisitus. They gave him saline drip for a few hours then sent him home with pain pills and doxycycline. Second time his diagnosis was just sinusitis, sent home with more pain pills. Third time, (another common diagnosis) the flu! He went back 2 times on the third day, and was refused a bed. I believe the phase was "you are not dying so you don't get a bed". Noticable on his admittance papers: his signature by the third admittance looked like he could no longer remember how to spell his name. He WAS given a CT scan each time, but for his chest. Blood work was also done, which did not match his diagnoses"
  and "Two days later he can not walk, hold any thing, is in horrible pain and very disoriented, seizing, hallucinating. He goes to a different ER. They decide that since my son drank beer daily that he was now in alcohol withdrawal. He is also in full blown kidney failure. They call three hospitals before they find one who can deal with his "withdrawal". He is admitted to the third hospital. Kidney failure dealt with and he is sedated"  Finally "Within 12 hours he has no gag reflex, no cough reflex, eyes not tracking or focusing. On life support. No reaction to pain. GCS is 12-14 for 3 days. No LP or MRI preformed yet. Yet they have decided to give him antibiotics and have diagnosed pneumonia. Admitted Sat, MRI finally done Tues. At this time it was discovered that he had massive swelling in his brain stem. He never came out of the coma and died after being on life support for 8 days. disturbances."(34)

B. Diagnosis
After taking the physical exam and medical history, depending to the symptoms of the patient and to rule out the similar symptoms with different diseases. In the report by the Royal Melbourne Hospital, Dr. Knox J, and the researchers indicated that a suspected but unproven case of Murray Valley encephalitis virus (MVEV) infection to illustrate some of the challenges in clinical management. It remains difficult to establish an early diagnosis of MVEV infection, and there is a lack of proven therapeutic options(35).
1. Brain Scans
Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI)
The aim of the test is to look for the extent inflammation of brain and rule out other similar symptoms of different diseases, including stroke, brain tumours, aneurysms, etc.

2. Electroencephalogram (EEG)
Electroencephalogram (EEG) is a measure of brain waves of that allow your doctor to see how your brain functions over a certain time. Any abnormal patten may provide evidence of in encephalitis, such as slowing of brain activity....

3. Lumbar puncture (LP)
Lumbar puncture (LP) or spinal tap is a diagnostic and at times therapeutic procedure allows a doctor to test the sample the cerebrospinal fluid (CSF) surrounded the brain and spinal cord and exam  under the microscope to assess the number and type of white blood cells in differentiation between viral or bacterial infections.

4. Serological tests
blood, urine, as well as other body fluids can also help to detect brain and/or spinal cord infection. Serological tests is the study of antibodies presented in the cerebrospinal fluid against a specific viral agent or by polymerase chain reaction that amplifies the RNA or DNA of the virus responsible.

5. Etc.

Preventions
A. Do's and Do not's list
1.  Behavioral
Delirious behavior associated with influenza usually has an onset within a few days after fever and lasts <24 hours. Dr. Takanashi J, and the research team showed that 2009 H1N1 influenza has a tendency to cause late-onset and long-standing delirious behavior, at least in Japanese children. Mild autoimmune-mediated encephalitis should be considered as an underlying cause.(36)

2. Eat your vegetable and fruits
Vegetable and fruit contain high amount of antioxidant, not only enhances the immune system but also fight against foreign virus and bacteria infection and inflammatory causes of meningitis(37)

3. Avoid excessive drinking
Excessive drinking can increase the risk of liver diseases that can lead to weaken immune function causes of meningitis


4. Moderate exercise
Moderate exercise can enhance the circulatory system and increase the function of immune system in fighting against bacterial and viral invasion.


5. Smoking
The odds ratio of purulent meningitis for children receiving passive smoking was 3.0, and the 95% confident limit was greater than 1 (P < 0.05). There was significant dose-effect relationship between the daily dosage of cigarette smoked by family members and the odds ratio of purulent meningitis (P < 0.005)(38)

6. Etc.

B. Diet against Encephalitis
A. Diet enhances the immune system and neuroprotectors should be helpful in preventing the occurrence of Encephalitis
A.1. Kidney beans
1. Antiradical and antioxidant activity
In the analyzing the effects of solid state fermentation (SSF) on physicochemical, nutritional and antioxidant properties of common bean flour found that tempeh flour had 2.2-fold more phenolics than the bean flour and exhibited antiradical activity (43%) and antioxidant activity (38%) correlated with total phenolics content. Common bean tempeh flour may be considered for the fortification of widely consumed legume-based food products and also for the prevention of pathologies associated with oxidative stress, according to "Physicochemical, nutritional and antioxidant properties of tempeh flour from common bean ( Phaseolus vulgaris L.)" by Reyes-Bastidas M, Reyes-Fernández EZ, López-Cervantes J, Milán-Carrillo J, Loarca-Piña GF, Reyes-Moreno C.(39)

2. Antioxidant and anti-inflammatory activities
In the study of Hulls obtained by mechanical abrasive dehulling from four bean and their antioxidant and anti-inflammatory activities, found that bean hull water extracts were stronger inhibitors of lipoxygenase, 15-LOX, than corresponding acetone extracts. Anti-inflammatory activity of bean hulls was dependent on their phenolic content and antioxidant activity that were significantly affected by cultivar and extracting solvent, according to "Antioxidant and anti-inflammatory activities of bean ( Phaseolus vulgaris L.) hulls" by Oomah BD, Corbé A, Balasubramanian P.(40)

3.  Immune system
Kidney bean contains eight basic form of amino acid which not only helps to the nervous system in relay information between themselves and cells in other parts of the body (according to the article of "Amino Acids: How They Affect the Brain and Nervous System" posted in http://www.greendivamom.com/) it also improves the immune system to generate B lymphocytes by rapid dividing and replicating for the body's antibody defense mechanism. In stuyd of "Branched-chain amino acid supplementation does not enhance athletic performance but affects muscle recovery and the immune system" by Negro M, Giardina S, Marzani B, Marzatico F., (41), researchers found that The BCAA (branched-chain amino acids) also modifies the pattern of exercise-related cytokine production, leading to a diversion of the lymphocyte immune response towards a Th1 type. According to these findings, it is possible to consider the BCAA as a useful supplement for muscle recovery and immune regulation for sports events.

A.2. Whole wheat
In the classification of Anthocyanins of whole purple wheat, unpolished red rice, and partially polished red rice before and after processing to produce infant cereals and it antioxidant efect found that purple wheat infant cereals had higher cellular antioxidant activity than unpolished red rice ones (p < 0.05). Whole purple wheat infant cereals showed higher antioxidant activity than the commercial infant cereal, suggesting a possibility of improving infant antioxidant status by incorporating this grain in their diet, according to "Comparative Evaluation of the Antioxidant Potential of Infant Cereals Produced from Purple Wheat and Red Rice Grains and LC-MS Analysis of Their Anthocyanins" by Hirawan R, Diehl-Jones W, Beta T.(42)


A.3. Eggplant
1. Antioxidant compounds
In the assessment of Thermal treatment of eggplant (Solanum melongena L.) and its effect on human neutrophil burst found that successive extract dilutions showed a significant activity up to 1.25 microg/mL after cooking, while raw fruits resulted in an activity up to 10.00 microg/mL. These results showed that the thermal treatment commonly used before consumption can increase the content and biological activity of antioxidant compounds of eggplants, according to "Thermal treatment of eggplant (Solanum melongena L.) increases the antioxidant content and the inhibitory effect on human neutrophil burst" by Lo Scalzo R, Fibiani M, Mennella G, Rotino GL, Dal Sasso M, Culici M, Spallino A, Braga PC.(43)

2.
Brain homogenates
In the classification ofAntioxidant activity of nasunin, an anthocyanin in eggplant peels and theirs effect on lipid peroxidation found that Nasunin protection against H(2)O(2)-induced lipid peroxidation in rat brain homogenate was measured at 586 nm using the indicator of malonaldehyde and 4-hydroxyalkenals. Nasunin (<50 microM) protected against lipid peroxidation of brain homogenates. The findings suggest that nasunin is a potent O(2)(-) scavenger and has protective activity against lipid peroxidation, according to "Antioxidant activity of nasunin, an anthocyanin in eggplant peels" by Noda Y, Kneyuki T, Igarashi K, Mori A, Packer L.(44)

A.4. White button mushrooms (WBM
1. Immunologic effects
In the analyzing White button mushrooms (WBM) and its effect in immune response, found that WBM promote DC maturation and enhance their antigen-presenting function. This effect may have potential in enhancing both innate and T cell-mediated immunity leading to a more efficient surveillance and defense mechanism against microbial invasion and tumor development, according to "White button mushroom enhances maturation of bone marrow-derived dendritic cells and their antigen presenting function in mice" by Ren Z, Guo Z, Meydani SN, Wu D.(45)

2. Neurotrophic action
Found that
the neurotrophic action of cobalamin (Cbl) in the central nervous system (CNS) of totally gastrectomized (TGX) rats is mediated by stimulation of the epidermal growth factor(EGF) synthesis in the CNS itself. It thus appears that Cbl inversely regulates the expression of EGF and TNF-alpha genes in the CNS of TGX rats, according to "Epidermal growth factor as a local mediator of the neurotrophic action of vitamin B(12) (cobalamin) in the rat central nervous system" by Scalabrino G, Nicolini G, Buccellato FR, Peracchi M, Tredici G, Manfridi A, Pravettoni G.(46)

3. Immune system
Since it contain high amount of vitamin C, it not only helps to improve the immune system in fighting against the foreign invasion, such as virus and bacteria, but also helps to inhibits fatty acid synthase expression as a result of the presence linoleic acid, thus reducing the risk of tumors and breast, colon and prostate cancers, according to the study of "The 10t,12c isomer of conjugated linoleic acid inhibits fatty acid synthase expression and enzyme activity in human breast, colon, and prostate cancer cells" by Lau DS, Archer MC.(47)

A.5. Garlic
1. Antioxidant effects
In the study of the Extracts of aged fresh garlic that are aged over a prolonged period and its antioxidant effects found that the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease, according to "Antioxidant health effects of aged garlic extract" by Borek C.(48)

2. Common cold
In the searched from January 1966 to September 2009 combining the key words common cold or influenza with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. Clinical trials and prospective studies found that for prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold, according to "Complementary and alternative medicine for prevention and treatment of the common cold" by Nahas R, Balla A.(49)

3. Tuberculosis
In the investigation of the garlic extracts and the increasing incidence of Mycobacterium tuberculosis (MTB) and particularly of multi-drug resistant tuberculosis (MDR-TB) found that Allium sativum offers a hope for developing alternative drugs. The involvement of traditional healers (TH) in the TB health management could facilitate the administration of garlic extracts to the infected patients, according to "The potential role of garlic (Allium sativum) against the multi-drug resistant tuberculosis pandemic: a review" by Dini C, Fabbri A, Geraci A.(50)

A.6. Tomato
1. Antioxidative and Cancer Cell-Inhibiting Activities
In the research of Tomato ( Solanum lycopersicum ) plants synthesize nutrients, pigments, and bioactive compounds and their benefit in nutrition and human health found that Tomato extracts promoted growth in normal liver (Chang) cells, had little effect in normal lung (Hel299) cells, mildly inhibited growth of lung cancer (A549) cells, and first promoted and then, at higher concentrations, inhibited growth in lymphoma (U937) cells. The relationship of cell growth to measured constituents was not apparent, according to "Free Amino Acid and Phenolic Contents and Antioxidative and Cancer Cell-Inhibiting Activities of Extracts of 11 Greenhouse-Grown Tomato Varieties and 13 Tomato-Based Foods" by Choi SH, Kim HR, Kim HJ, Lee IS, Kozukue N, Levin CE, Friedman M.(51)

2. Lycopene
Lycopene, one of the powerful antioxidant in tomatoes, not only helps the immune system in neutralizing the forming of free radicals in the body and according to Harvard investigation as it found that men who ate more than 10 servings tomato-based foods daily (like cooked tomatoes and tomato sauce,) had a 35 percent lower risk of developing prostate cancer than those who ate the least amount of these foods. The benefits of lycopene was more pronounced with advanced stages of prostate cancer. Also according to the study of "Chemoprevention of prostate cancer with lycopene in the TRAMP model" by Konijeti R, Henning S, Moro A, Sheikh A, Elashoff D, Shapiro A, Ku M, Said JW, Heber D, Cohen P, Aronson WJ.(52)

2. Antiaging
Tomato beside prevents the progressive loss of structure, function or death of neurons, including Parkinson’s, Alzheimer’s, and Huntington’s diseases, According to the study of "Role of oxidative stress and antioxidants in neurodegenerative diseases" by Rao AV, Balachandran B(53), it also contains vitamin C that helps to releases of histamine (local immune responses), thus increasing the detoxification of histamine, according to the study of "Effect of ascorbic acid on histamine metabolism in scorbutic guinea-pigs" by I B Chatterjee, S D Gupta, A K Majumder, B K Nandi, and N Subramanian, posted in (54) researchers indicated that The increased histamine content of the urine, blood and other tissues in the ascorbic-acid-depleted condition could be brought back to normal levels by administration of a single dose of ascorbic acid 5 mg/100 g body wt.

3. Detoxification
Liver is a second defense that helps to clean out the toxins accumulation in the blood body. If the liver is over work, it can cause liver congestion, leading to lower of bile production or weaken carbohydrate metabolism. Since tomato contains high amount of Vitamins A and C, it not only supports liver function but stimulates the liver's function in detoxification of toxins., according to the study of "Effects of dried fish on antioxidant levels in rat liver" by Anilakumar KR, Khanum F, Krishna KR, Viswanathan KR.(55)

A.7. Blueberry
In the investigation of Blueberry and blackberry wines commercially available in Illinois and theirs potential health benefits, found that fruit wines made from blueberries and blackberries may have potential health applications and therefore could contribute to the economy of the wine industry. Practical Application: The majority of wines are produced from grapes, but wine can also be produced from other fruits including blueberries and blackberries, which contain phenolic compounds that may contribute to human health, according to "Comparison of Chemical Composition and Antioxidant Capacity of Commercially Available Blueberry and Blackberry Wines in Illinois" by Johnson MH, Gonzalez de Mejia E.(56)

A.8. Raspberries
1. Neurodegenerative diseases
In the identification of Resveratrol found skin of grapes, raspberries, mulberries, pistachios and peanuts and theirs effect neurodegenerative diseases, found that resveratrol shows effects in in vitro models of epilepsy, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and nerve injury. However, evidences in vivo as well as in human beings are still lacking. Thus, further investigations on the pharmacological effects of resveratrol in vivo are necessary before any conclusions on its effects on neurodegenerative diseases can be obtained, according to "Resveratrol: a natural compound with pharmacological potential in neurodegenerative diseases" by Rocha-González HI, Ambriz-Tututi M, Granados-Soto V.(57)

2. Degenerative diseases of ageing
Long-term vitamin K inadequacy may reduce the function of supporting the carboxylation of at least some of these Gla-protein that can lead the development of degenerative diseases of ageing including osteoporosis and atherosclerosis, according to the study of "Vitamin K, osteoporosis and degenerative diseases of ageing" by Cees Vermeer and Elke Theuwissen(58)

3.  Antioxidant
Vitamin C or ascorbic acid is a powerful antioxidant which inhibits the forming of the free radical due to oxidative stress. It also enhances the function of immune system in guarding our body against foreign invasion, thus reducing the risk of inflammatory and infectious diseases, according to the study of "Role of ascorbic acid in scavenging free radicals and lead toxicity from biosystems" by Tariq SA.(59)
 
A.9 Flax seed
Flax seed contains a high amount of antioxidant that helps to guard the body from forming of free radicals by promoting the proper DNA replication and cells division, according to "Free radicals, metals and antioxidants in oxidative stress-induced cancer" by Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M.(60) 
 
A.10. Salmon
1. Antioxidants
In the research of the antioxidant effect of vitamin E after ingestion of salmon found that that megadoses of vitamin E, far from having pro-oxidative activity, actually increase the anti-oxidative capacity of the liver, especially after ingestion of salmon oil, according to "Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed lard or salmon oil" by Flader D, Brandsch C, Hirche F, Eder K.(61)
 
2. Selenium
Salmon contains trace minerals selenium which is essential for the healthy function of the thyroid and immune system as it increases the antioxidant defense system by fighting against the forming of free radicals and reduce the risk of irregular cells growth causes of tumor and cancer, according to the study of "Selenium in the immune system" by Arthur JR, McKenzie RC, Beckett GJ., posted in PubMed (62)
 
3. Anti inflammationIt is said the Omega 3 fatty acids beside reduced the risk of inflammatory effects on our joints and improved blood flow, by regulating the migration of inflammatory cells that cause inflammation, but also autoimmune diseases as a result of the elevation of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids, according to the study of "Omega-3 fatty acids in inflammation and autoimmune diseases" by Simopoulos AP., (63) 
 
A.11. Etc.
 

C. Nutritional supplements against Encephalitis(64)
Nutritional supplements enhances the immune system and neuroprotectors should be helpful in preventing the occurrence of Encephalitis
1. Bilirubin
Bilirubin is a prosthetic group which helps to break down molecules into smaller units in releasing energy, excreted in bile and urine. It is a cellular antioxidant, by reverting to biliverdin, a green tetrapyrrolic bile pigment, once again when oxidized that inhibits the effects of mutagens.

2. Carotenoids
Carotenoids are organic pigments, occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria.
a. Beta-carotene
Beta-Carotene, an organic compound and classified as a terpenoid, a strongly-coloured red-orange pigment in plants and fruits.
a.1. It is not toxic and stored in liver for the production of vitamin A that inhibits cancer cell in experiment. Beta-carotene also neutralize singlet oxygen before giving rise of free radicals which can damage of DNA, leading to improper cell DNA replication, causing cancers.
a.2. Cell communication
Researcher found that beta-carotene enhances the communication between cell can reduce the risk of cancer by making cells division more reliable.
a.3. Immune system
Beta-carotene promotes the immune system in identifying the foreign invasion such as virus and bacteria by increasing the quality of MHC2 protein in maintaining optimal function of white cells.
a.4. Polyunsaturated fat
Researchers found that beta-carotene also inhibits the oxidation of polyunsaturated fat and lipoprotein in the blood that reduce the risk of plaques build up onto the arterial walls, causing heart diseases and stroke.
a.5. There are more benefits of beta-carotene.

b. Alpha-carotene
Alpha-carotene, one of the most abundant carotenoids in the North American diet, is a form of carotene with a β-ring at one end and an ε-ring at the other. It is the second most common form of carotene which not only protects cells from the damaging effects of free radicals and enhances the immune system in fighting against bacteria and virus invasion, but also stimulates the communication between cells thus preventing irregular cell growth cause of cancers.

c. Beta-cryptoxanthin
Beta cryptoxanthin is an antioxidant, beside helping to prevent free radical damage to cells and DNA but also stimulates the repair of oxidative damage to DNA. it enhances the immune function infighting against inflammatory cause of polyarthritis, and irregular cell growth cause of cancer due to oxidation.

d. Lutein
Lutein is one of the most popular North American carotenoids. It is found in greens like kale and spinach as well as the yolk of eggs. Lutein is also found in the human eye. Getting enough lutein in your diet may help to fight off age related macular degeneration, an eye condition.
Researcher has shown that people who do not have enough lutein in their diet will not have enough lutein present in the muscular part of the eye. This is what likely leads to age related macular degeneration that can result in blindness.

e. Zeaxanthin
Zeaxanthin, a most common carotenoid alcohols found in nature, is one of the two primary xanthophyll carotenoids contained within the retina of the eye. Intake of foods providing zeaxanthin with lower incidence of age-related macular degeneration as a result of its function of reducing the risk oxidative stress.

f. Lycopene
Lycopene is a red carotene of the carotenoid group that can be found in tomatoes, watermelons, and grapefruits. This powerful antioxidant is believed to be a powerful fighter of prostate cancer. Lycopene has many anti-aging capabilities as well as one of the most powerful antioxidants in the carotenoid group.

3. Flavonoids
Flavonoids also known as Vitamin P and citrin are a yellow pigments having a structure similar to that of flavones occurred in varies plants. it has been in human history for over thousands of years and discovered by A. S. Szent-Gyorgi in 1930. As he used vitamin C and flavonoids to heal the breakage of capillaries, which caused swelling and obstruction of blood flow. Most plants have more than one group or type act as predominate.
Flavonoids process a property as antioxidants. it helps to neutralize many of reactive oxygen species (ROS), including singlet oxygen, hydroxyl and superoxide radicals.
Although nitric oxide is considered a free radical produced by immune system to destroy bacteria and cancerous cells, but when it is over produced, it causes the production peroxynitrite which may attack protein, lipid and DNA, Flavonoids inhibit NO production of peroxynitrite due to reduction of enzyme expression.
a. Quercetin
Quercetin is a plant-derived flavonoid found in fruits, vegetables, leaves and grains and studies show that quercetin may have anti-inflammatory and antioxidant properties as a antioxidant, quercetin scavenges free radicals, which damage cell membranes, cause mutation of cells with tampering DNA.

b. Rutin
Rutin is a citrus flavonoid glycoside found in buckwheat and glycoside of the flavonoid quercetin. It inhibits platelet aggregation, decreases the capillary permeability, makes blood thinner and improves circulation. As an antioxidant, it can reduce the cytotoxicity of oxidized LDL cholesterol caused by free radical that lowers the risk of heart diseases.

c. Catechin
Catechin is a natural phenol antioxidant plant and natural anti-bacterial substance. Study showed catechin as good free radical scavenging power inhibits ROS production, thus it can be useful to the development of alimentary strategies to prevent OTA-induced cytotoxicity in human.

d. Etc.

4. Uric acids
Uric acids may have a potential therapeutic role as an antioxidant becuase of its function of inducing oxidative stress, either through creating reactive oxygen species or inhibiting antioxidant systems.
High uric acid can cause arthritis, cardiovascular disease, diabetes, Metabolic syndrome, kidney stones, etc.

5. Thiols (R-SH)
Chemically, thiol, a organosulfur compound has strong odours resembling that of garlic. They are used as odourants to assist in the detection of natural gas. It presents in the amino acid cysseine which helps to the functioning of enzyme regulation, cell signaling, protein trafficking and control of gene expression. As a sulfide residue, thiol plays an important role in cell function of reversal oxidation by interacting with GSSG resulting in formation of intramucolar protein disulfide and GSG.

6. Coenzyme Q10
Coenzyme Q10 is discovered by Dr. Karl Folfers in 1957, beside promotes the chemical reaction, often by speeding it up or allowing it to proceed under less stringent conditions, it also enhances energy production by promoting the process of the production of ATP then serving as fuel for the cells and acts an antioxidant to prevent the generation of free radicals during this process.

7. Vitamin A, C, E. D.
a. Vitamin A
Vitamin A occurs in the form retinol and is best known for its function in maintaining the health of cell membrane, hair, skin, bone, teeth and eyes. It also plays an important role as an antioxidant as it scavenges free radicals in the lining of the mouth and lungs; prevents its depletion in fighting the increased free radicals activity by radiation; boosts immune system in controlling of free radicals; prevents oxidation of LDL and enhances the productions of insulin pancreas.

b. Vitamin C
Vitamin C beside plays an important role in formation and maintenance of body tissues, it as an antioxidant and water soluble vitamin, vitamin C can be easily carry in blood, operate in much of the part of body. By restoring vitamin E, it helps to fight against forming of free radicals. By enhancing the immune system, it promotes against the microbial and viral and irregular cell growth causes of infection and inflammation.
Vitamin C also is a scavenger in inhibiting pollution cause of oxidation.

c. Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols discovered by researchers Herbert Evans and Katherine Bishop. It beside is important in protecting muscle weakness, repair damage tissues, lower blood pressure and inducing blood clotting in healing wound, etc, it also is one of powerful antioxidant, by moving into the fatty medium to prevent lipid peroxidation, resulting in lessening the risk of chain reactions by curtailing them before they can starts.

d. Vitamin D
Reseacher found that vitamin D, a group of fat-soluble secosteroids is also a membrane antioxidant, with the ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol.


D. Phytochemicals against Encephalitis
Phytochemicals enhances the immune system and promote cognitive effect should be helpful in preventing the occurrence of Encephalitis
D.1. Carnosol 
1. Anti-inflammatory effects
In the study of The increased adhesion of monocytes to injured endothelial layers and the effect of carnosol and rosemary essential oils found that the essential oil inhibit the adhesion of TNFalpha-induced monocytes to endothelial cells and suppress the expression of ICAM-1 at the transcriptional level, according to "Dual mechanisms of NF-kappaB inhibition in carnosol-treated endothelial cells" by Lian KC, Chuang JJ, Hsieh CW, Wung BS, Huang GD, Jian TY, Sun YW(65)

2. Antimicrobial activity
In the determination of EtOH/H2O extracts from the leaves and stems of Rosmarinus officinalis L and it antimicrobial effects found that antimicrobial activity of the extract from the leaves of R. officinalis may be ascribed mainly to the action of carnosic acid (2) and carnosol (3), according to "Antimicrobial activity of Rosmarinus officinalis against oral pathogens: relevance of carnosic acid and carnosol' by Bernardes WA, Lucarini R, Tozatti MG, Souza MG, Silva ML, Filho AA, Martins CH, Crotti AE, Pauletti PM, Groppo M, Cunha WR.(66)

D.2. Quercetin is a member of flavonoids, found in fruits, vegetables, leaves and grains. It is also one of antioxidants with property of protecting our body in fighting against forming of free radicals cause of mutation of cells`DNA.
1. Oxidative Stress
According to the study of `The protective effect of the flavonoids on food-mutagen-induced DNA damage in peripheral blood lymphocytes from colon cancer patients.`by Kurzawa-Zegota M, Najafzadeh M, Baumgartner A, Anderson D. (Source from Genetic and Reproductive Toxicology Group, Division of Biomedical Sciences, University of Bradford, Bradford BD7 1DP, UK.) posted in PubMed, researchers found that flavonoids (quercetin (Q) and rutin (R)) reduced oxidative stress caused by food mutagens in vitro in lymphocytes of healthy individuals and colon cancer patients. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protecting against oxidative stress.

2. Anti-cytogenotoxic effects
In a study of `Assessment of anti-cytogenotoxic effects of quercetin in animals treated with topotecan.`by Bakheet SA. (Source from Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. 2457, Riyadh 11451, Saudi Arabia.), posted in PubMed, researchers found that quercetin has a protective role in the abatement of topotecan-induced cyto- and genotoxicity in the bone marrow cells of mice that resides, at least in part, on its antioxidant effects. Based on the data presented, strategies can be developed to decrease the topotecan-induced bone marrow suppression and secondary malignancy in cancer patients and medical personnel exposing to topotecan.

3. Free radical scavenger
In a study of `Dietary chromones as antioxidant agents-the structural variable.`by Dias MM, Machado NF, Marques MP. (Source from Research Unit "Molecular Physical Chemistry", University of Coimbra, Portugal.), posted in PubMed, researchers found that from the eighteen tested compounds, three-fisetin, luteolin and quercetin-are shown to act as effective antiradicals. Consistent structure-activity relationships (SARs) were established regarding the antioxidant role of this type of chromone-based system. 

D.3. Tangeritin, one of the flavones, is found in tangerine and many citrus peels
1. Neuroprotective effects
In the evaluation of neuroprotective effects of a natural antioxidant tangeretin, a citrus flavonoid and its effect on Parkinson's disease found that tangeretin crosses the blood-brain barrier. The significant protection of striato-nigral integrity and functionality by tangeretin suggests its potential use as a neuroprotective agent, according to "Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease" by Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT.(67) 

2. Antioxidants
In the comparison of hand-pressed juice of polymethoxylated flavones (PMFs) and flavanone glycosides (FGs) and the peeled fruit of 'Sainampueng' tangerines ( Citrus reticulata Blanco cv. Sainampueng) antioxidant effects found that hand-pressed juice of C. reticulata Blanco cv. Sainampueng serves as a rich source of PMFs, FGs, carotenoids, and antioxidants: 4-5 tangerine fruits ( approximately 80 g of each fruit) giving one glass of 200 mL hand-pressed juice would provide more than 5 mg of nobiletin and tangeretin and 36 mg of hesperidin, narirutin, and didymin, as well as 30 mg of ascorbic acid, >1 mg of provitamin A active beta-cryptoxanthin, and 200 microg of alpha-tocopherol, according to "Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines ( Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand" by Stuetz W, Prapamontol T, Hongsibsong S, Biesalski HK.(68)

3. Antimicrobial activity
In the study of antibacterial and antifungal properties of wax and hexane extracts of Citrus spp. peels found that antimicrobial activity especially against M. canis and T. mentagrophytes: 4',5,6,7,8-pentamethoxyflavone (tangeritin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) from C. reticulata; and 6,7-dimethoxycoumarin (also known as escoparone, scoparone or scoparin) from C. limon, according to "Antimicrobial activity of wax and hexane extracts from Citrus spp. peels" by Johann S, Oliveira VL, Pizzolatti MG, Schripsema J, Braz-Filho R, Branco A, Smânia Jr A.(69)

D.4. Catechin is phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in white tea, green tea, black tea, grapes, wine, apple juice, cocoa, lentils, etc.
1. Antioxidant activity
In the research on polyphenolic compounds (included catechins) in the berries of edible honeysuckle and their biological effects, including recommended utilization, are reviewed found that These berries seem to be prospective sources of health-supporting phytochemicals that exhibit beneficial anti-adherence and chemo-protective activities, thus they may provide protection against a number of chronic conditions, e.g., cancer, diabetes mellitus, tumour growth or cardiovascular and neurodegenerative diseases, according to "Phenolic profile of edible honeysuckle berries (genus lonicera) and their biological effects" by Jurikova T, Rop O, Mlcek J, Sochor J, Balla S, Szekeres L, Hegedusova A, Hubalek J, Adam V, Kizek R.(70)

2. Anti-inflammatory effect
In the preparation of the gel of Chinese medicine catechu, and to observe the release mechanism in vitro and anti-inflammatory activity in rats, found that the optimum condition of extraction from catechu was as follows, the concentration of ethanol, ratio of raw material to solvent, ultrasonic time, and extraction temperature were 50% , 1: 12, 35 min and 60 degrees C, respectively. The formulation of catechu gel was carbomer-9 400.5 g, glycerol 5.0 g, the extracts of catechu 50.0 mL, and triethanomine 0.5 mL The gel was semitransparent and stable. The drugs released quickly. The catechu gel reduced the paw edema considerably in dose-dependent manner compared to carrageenan-induced rat, according to "[Preparation and pharmacodynamics studies on anti-inflammatory effect of catechu gel].[Article in Chinese]" by Zheng X, Zheng C.(71)

3. Neuropathic pain
In the investigation of Epigallocatechin-3-gallate (EGCG), the major catechin in green tea and its effect on intrathecal EGCG in neuropathic pain induced by spinal nerve ligation, found that This antinociceptive effect was reversed by intrathecal pretreatment with l-arginine, a precursor of NO. Intrathecal EGCG also blocked the increase in nNOS expression in the spinal cord of spinal nerve-ligated rats, but iNOS expression was not significantly suppressed. These findings suggest that intrathecal EGCG could produce an antiallodynic effect against spinal nerve ligation-induced neuropathic pain, mediated by blockade of nNOS protein expression and inhibition of the pronociceptive effects of NO, according to "Role of neuronal nitric oxide synthase in the antiallodynic effects of intrathecal EGCG in a neuropathic pain rat model" by Choi JI, Kim WM, Lee HG, Kim YO, Yoon MH.(72)

4. Anti-influenza virus activity
In the study of Polyphenolic compounds present in green tea, particularly catechins, and its effect on strong anti-influenza activity, found that therapeutic administration of green tea by-products via feed or water supplement resulted in a dose-dependent significant antiviral effect in chickens, with a dose of 10 g/kg of feed being the most effective (P < 0.001), according to "Anti-influenza virus activity of green tea by-products in vitro and efficacy against influenza virus infection in chickens" by Lee HJ, Lee YN, Youn HN, Lee DH, Kwak JH, Seong BL, Lee JB, Park SY, Choi IS, Song CS.(73)

D.5. Ellagic acid
1. Antiproliferative and Antioxidant
In a study of " In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice" by Navindra P. Seerama, Lynn S. Adamsa, Susanne M. Henninga, Yantao Niua, Yanjun Zhangbc, Muraleedharan G. Nairbc, David Hebera (Volume 16, Issue 6, Pages 360-367 (June 2005)), posted in The journal of Ntritional Biochemitry, researchers indicated that Antioxidant effects were evaluated using inhibition of lipid peroxidation and Trolox equivalent antioxidant capacity (TEAC) assays. Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 μg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action

2. Oxidative stress
According to the article of "BIOLOGICAL FUNCTIONALITY OF ELLAGIC ACID: A REVIEW" by D.A. VATTEM and K. SHETTY , Article first published online: 30 JUN 2005, posted in Wiley Online Library, researchers indicated that in abstract, in this article, we have revised the existing models and have proposed a comprehensive model for the antioxidant response-linked mechanism of the action of ellagic acid from fruits at the early stages of host cellular response by the modulation of enzyme response to maintain cellular homeostasis in eukaryotes and by inhibiting the survival in pathogenic prokaryotes.

3. Anti-inflammation
In a study of " Antinociceptive effect of Lafoensia pacari A. St.-Hil. independent of anti-inflammatory activity of ellagic acid. by Nascimento MV, Galdino PM, Florentino IF, Sampaio BL, Vanderlinde FA, de Paula JR, Costa EA. (Source from Instituto de Ciências Biológicas-2, Universidade Federal de Goiás, Goiânia, Brazil. nascimentofarma@yahoo.com.br) posted in PubMed. researchers found that Pre-treatment with naloxone did not reverse the antinociceptive effect. Only the ethyl acetate fraction showed antinociceptive and anti-inflammatory effects. Our results also showed that this extract contains compounds with analgesic action independent of anti-inflammatory activity.

D.6. Stilbenoids are type of chemical compound, belonging to the family of phenylpropanoids, including Resveratrol, Pterostilbene and Piceatannol found in grape skins and seeds, wine, nuts, peanuts, etc., According to the article of "Production of stilbenoids and phenolic acids by the peanut plant at early stages of growth." by Sobolev VS, Horn BW, Potter TL, Deyrup ST, Gloer JB. (Source from National Peanut Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, P.O. Box 509, Dawson, Georgia 39842, USA. vsobolev@nprl.usda.gov), posted in PubMed.
 1. Neuroprotective Activity
in a study of "Neuroprotective effect of resveratrol against methamphetamine-induced dopaminergic apoptotic cell death in a cell culture model of neurotoxicity" by Kanthasamy K, Gordon R, Jin H, Anantharam V, Ali S, Kanthasamy AG, Kanthasamy A. (Source from Dept. of Biomedical Sciences, Iowa Center for Advanced Neurotoxicology, Iowa State University, Ames, IA 50011-1250.), posted in PubMed, researchers mentioned in abstract that . Notably, treatment with resveratrol almost completely attenuated MA-induced caspase-3 activity, but only partially reduced apoptotic cell death. We conclude that the neuroprotective effect of resveratrol is at least in part mediated by suppression of caspase-3 dependent cell death pathways. Collectively, our results demonstrate that resveratrol can attenuate MA-induced apoptotic cell death and suggest that resveratrol or its analogs may have therapeutic benefits in mitigating MA-induced dopaminergic neurodegeneration.

2. Anti-Inflammation
In a study of "Resveratrol, MicroRNAs, Inflammation, and Cancer." by Tili E, Michaille JJ. (Source from Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Biomedical Research Tower, 460 W 12th Avenue, Columbus, OH 43210, USA.), posted in PubMed, researchers mentioned in abstract that the above microRNAs are thought to link inflammation and cancer. Recently, resveratrol (trans-3,4',5-trihydroxystilbene), a natural polyphenol with antioxidant, anti-inflammatory, and anticancer properties, currently at the stage of preclinical studies for human cancer prevention, has been shown to induce the expression of miR-663, a tumor-suppressor and anti-inflammatory microRNA, while downregulating miR-155 and miR-21.

3. Oxidative stress
In a study of " Resveratrol up-regulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights." by Yun JM, Chien A, Jialal I, Devaraj S. (Copyright © 2011 Elsevier Inc. All rights reserved.), reseachers wrote in abstract that In this study, we tested the protective effect of resveratrol on cellular oxidative stress through the SIRT1-FOXO pathway under high-glucose conditions. Human monocytic (THP-1) cells were cultured in the presence of mannitol (osmolar control) or normoglycemic (NG, 5.5 mmol/l glucose) or hyperglycemic (HG, 25 mmol/l glucose) conditions in absence or presence of resveratrol (3 and 6 μmol/l) for 48 h. We first examined SIRT1 activity and oxidative stress in monocytes of Type 1 diabetes mellitus (T1DM) patients compared with healthy controls. In T1DM patients, monocytic SIRT1 expression was significantly decreased and p47phox expression was increased compared with controls. Under HG in vitro, SIRT1 and FOXO3a were significantly decreased compared with NG, and this was reversed by resveratrol treatment, concomitant with reduction in HG-induced superoxide production and p47phox. Under HG, SIRT1 small interfering RNA (siRNA) inhibited FOXO3a, and there was no beneficial effect of resveratrol in siRNA-treated HG-induced cells.

D.7. Etc.

Treatments
A. In conventional medicine perspective
There are no specific medications to treat encephalitis, most common antiviral medication used is acyclovir (Zovirax). Depending to the specific symptoms, the following medication are recommended
1. Acyclovir (Zovirax) -- treats encephalitis against HSV, VZV, and EBV
In the study to tested for activity in vitro against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), human and murine cytomegalovirus (HCMV and MCMV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV), Dr. Kern ER, adn the research team at theUniversity of Alabama at Birmingham shoowed that these compounds [A second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and 18 compounds] were tested for activity in vitro against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), human and murine cytomegalovirus (HCMV and MCMV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV) are phosphorylated by the ppUL97 phosphotransferase and are potent inhibitors of viral DNA synthesis. These results indicate that at least one of these compounds may have potential for use in treating CMV and other herpesvirus infections in humans(74)

2. Ganciclovir (Cytovene) treats encephalitis agaimst cytomegalovirus and HSV1
In the study to report a case of recurrent cytomegalovirus (CMV) corneal endotheliitis after penetrating keratoplasty, scientists at the  Taipei City Hospital showed that CMV DNA was detected from the excised corneal button, and aqueous humor revealed positive results for CMV and HSV1 by PCR. Confocal microscopy showed large corneal endothelial cells, consistent with the typical owl's eye morphology of CMV endotheliitis. After systemic ganciclovir was administered, the pigmented KPs and coin-shaped lesions gradually decreased(75)

3. Antiepileptic drug -- treat against seizures associated with encephalitis
In the study to pressing need for consistent, evidence-based guidelines in the management of neonatal seizures by pediatric, neurologists and neonatologists, neurologists and neonatologists at the Tel Aviv Sourasky Medical Center and Sackler School of Medicine completed a 20-item, self-administered questionnaire on choices of antiepileptic drugs, treatment of intractable neonatal seizures (unremitting seizures after 3 medications), treatment duration, and recommended workup. The responding 36/55 (65%) neurologists and 66/112 (59%) neonatologists made similar  choices (phenobarbital as first line, phenytoin as second line, and benzodiazepines as third line), called for controlled clinical trials to establish protocols for (1) diagnosing neonatal seizures, (2) studying the efficacy and safety of new-generation antiepileptic drugs, and (3) determining optimal duration of drug administration(76).

4. Etc.

B. In herbal perspective
B.1. Green tea (Camellia sinensis)
1. Immune systemIn the investigation of the immunomodulatory effects of decaffeinated green tea extract in rain bow of the study of "Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK, researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout(77).

2. Antimicrobial activities
In the investigation of Antimicrobial activities of green of the study of "Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus" by Friedman M, Henika PR, Levin CE, Mandrell RE, Kozukue N., researchers found that flavonoids in green tea has exerted its ability in protective effects against Bacillus cereus(78).

3. Antioxidant activity
In the determination of Green and black tea polyphenols and their strong antioxidant activity of the study of "Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement" by Henning SM, Niu Y, Lee NH, Thames GD, Minutti RR, Wang H, Go VL, Heber D., researchers concluded that green tea extract supplements retain the beneficial effects of green and black tea and may be used in future chemoprevention studies to provide a large dose of tea polyphenols without the side effects of caffeine associated with green and black tea beverages(79).

B.2. Cat's claw (Uncaria tomentosa)
1. Anti-inflammatory and antioxidant activities
Oral extract of Cat's claw has demonstrated the activity of protection against indomethacin-induced gastritis, and prevention of TNFalpha mRNA expression and apoptosis, according to the study of `Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content`by Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles' FM, Musah RA, Bobrowski P, Miller MJ.(80)

2. Antimicrobial activity
Cat`s claw has exerted antimicrobial activity against microorganisms frequently found in infected root-filled teeth, including Enterococcus faecalis, Staphylococcus aureus, and Candida albicans, according to the study of `In vitro antimicrobial activity of phytotherapic Uncaria tomentosa against endodontic pathogens`by Herrera DR, Tay LY, Rezende EC, Kozlowski VA Jr, Santos EB(81)

3. Garlic (Allium sativum)
In the study of the Extracts of aged fresh garlic that are aged over a prolonged period and its antioxidant effects found that the ability of AGE to protect against oxidant-induced disease, acute damage from aging, radiation and chemical exposure, and long-term toxic damage. Although additional observations are warranted in humans, compelling evidence supports the beneficial health effects attributed to AGE, i.e., reducing the risk of cardiovascular disease, stroke, cancer and aging, including the oxidant-mediated brain cell damage that is implicated in Alzheimer's disease, according to "Antioxidant health effects of aged garlic extract" by Borek C.(48)

B.4. Astragalus (Astragalus membranaceus)
1. Immune system
Astragalus polysaccharides (APS) isolated from astragalus enhances the immune system by enhancing and regulating the function of T cells, by suppressing the CD4(+)CD25(+)Treg activity, at least in part, via binding TLR4 on Tregs and trigger a shift of Th2 to Th1, according to the study of "Astragalus polysaccharides attenuate postburn sepsis via inhibiting negative immunoregulation of CD4+ CD25(high) T cells" by Liu QY, Yao YM, Yu Y, Dong N, Sheng ZY., posted in PubMed(82)

2. Anti-inflammation
Astragalus has exerted an anti-inflammatory effect as a result of inactivation the p38 and Erk1/2 and inhibition NFkappaB-mediated transcription, according to the study of "Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk" by Ryu M, Kim EH, Chun M, Kang S, Shim B, Yu YB, Jeong G, Lee JS., posted in PubMed(83)

B.5. Elder (Sambucus)
1. Immunostimulatory propertie
In the study of five herbal remedies--Sambucol Black Elderberry Extract, Sambucol Active Defense Formula and Sambucol for Kids (with known antiviral properties), Protec and Chizukit N (containing propolis and Echinacea, claimed to be immune enhancers) and their anti-inflammatory cytokines effects found that The three Sambucol formulations activate the healthy immune system by increasing inflammatory and anti-inflammatory cytokines production, while the effect of Protec and Chizukit N is much less. Sambucol could therefore have immunostimulatory properties when administered to patients suffering from influenza (as shown before), or immunodepressed cancer or AIDS patients who are receiving chemotherapy or other treatments, according to "The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines" by Barak V, Birkenfeld S, Halperin T, Kalickman I.(84)

2. Anti-inflammatory effects
In the demonstration of Mucin-specific lectin from Sambucus sieboldiana (SSA-M) and it effect onanti- chronically inflammatory diseases found that an additional mechanism of the anti-inflammatory activity of ursolic acid by demonstrating its ability to inhibit TNFα-stimulated expression of VCAM-1 and ICAM-1 and support the traditional use of extracts and preparations of Sambucus ebulus L., rich in ursolic acid, for the treatment of chronically inflammatory processes, according to "Identification and pharmacological characterization of the anti-inflammatory principal of the leaves of dwarf elder (Sambucus ebulus L.)" by Schwaiger S, Zeller I, Pölzelbauer P, Frotschnig S, Laufer G, Messner B, Pieri V, Stuppner H, Bernhard D.(85)

B.6. Etc.
 
C. In Chinese medicine perspective(86)
Traditional Chinese medicine defined Encephalitis as a condition of  acute febrile disease as pathogenic warm factor entering the body, or invasion of the heat into the pericardium, or disturbance of the heart by phlegmatic fire or the inward invasion of the weak wind.
C.1. Encephalitis as Pathogenic warm factor entering the body
1. Symptoms are not limit to
Fever, headache, perspiration, chilly sensation, pain of the throat, thirst, stiffness of the neck, mental confusion, delirium, convulsions, thin white or slight yellowish coating of the tongue and rapid pulsem etc.

2. The formula  Bai Hu Tang Jia Jian. The aim is to purify the Qi with pungent-cold drugs and to detoxify the body. Ingredients include
      Gypsum 60g,
      Root of Zhejiang figwort 30,
     Tuber of dwarf lilyturf 30g
     Fresh or dried rehmannia 30g
     Rhizome of wind-weed 12g
     Honeysuckle flower 30g
     Weeping forsythia (fruit) 30g
     Common red rhizome 30g
     Dryers woad root  30g
     Dryers woad leaf 30g
     Cicada slough  20g
     Larva of a silkworm with batrytis  10g
     Licorice root  6g



C.2. Encephalitis as invasion of the heat into the pericardium
1. Symptoms are nor limit to
Fever, headache, mental confusion, stupor, delirium, tremors, yellow coating of the tongue with dark red colour, and full pulse, etc.
2.  The fomula Qing Ying Tang Jia Jian. The aim is to to purge the pathogenic fire and calm the wind with Qing Ying Tang Jia Jian. In gredients include
 
     Gypsum 60g
     Rhizome of wind-weed 12g
     Fresh or dried rehmannia 20g
     Root of Zhejiang figwort 30g
     Root-bark of peony 15g
     Dyers woad root  30g
     Dyers woad leaf 30g
     Rhubarb  10g
     Jack-in-the-pulpit 12g
     Tabasheer 12g
     Earthworm 15g
     Scorpion  15 pieces
     Centipede 1 or 2 pieces
      Buffalo horn  30g
 
C. 3. Encephalitis as disturbance of the heart by phlegmatic fire.
1. Symptoms are not limit to
Mental confusion, delirium, mania and excitability, or spitting sputum and saliva, red tongue with yellowish and glossy coating, slippery and rapid pulse, etc.
2. The formula Dao Tan Tang Jia Jian. The aim is to reduce phlegm for resuscitation. Ingredients include
      Dried old orange peel  12g
      Pinellia  12g
      Tuckahoe  10g
      Licorice root 6g
      Jack-in-the-pulpit 12g
      Fruit of immature citron or trifoliate orange  12g
      Tabasheer 12g
      Grass-leaved sweetflag  12g
      Root-tuber of aromatic turmeric  12g
      Bamboo shavings  12g
      Musk  0.06g
      Bamboo juice 3 or 4 spoonful

D.  Encephalitis as the inward invasion of the weak wind.
1. Symptoms are not limit to
Dizziness, convulsions or tremor, flushed face, hot palms and soles, dysphoria, restlessness, insomnia, dry throat and mouth, dark red tongue with reduced saliva, weak and rapid pulse.

2. The formula Da Ding Feng Zu Tang Jia Jian. The aim is  to calm the "wind" through nourishing the Yin. Ingredients include
     Root of herbaceous  30g
     Donkey-hide gelatin  12g
     Tortoise plastron 20g
     Dried rehmannia 20g
     Fructus cannabis 20g
     Fruit of Chinese magnaliavine 20g
     Tuber of dwarf lilyturf 30g
     Oyster 30g
     Turtle-shell 30g
     Radix glycyrrhizae 6g
     Egg core 6g


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