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Iranian researchers claim thyme, other plant extracts may prevent, treat COVID-19

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•Compound found in herbs, berries, fruits prevents, reverses brain damage linked to Parkinson’s disease
•Abstinence from smoking, drinking, low body mass index, exercise may help mitigate high genetic risk of cancer

Researchers have in recent studies validated more local plants that can be used to prevent and treat COVID-19. They concluded that numerous medicinal plants such as lime, lemon, oranges, grapefruit, green tea, thyme and garlic can interference with COVID-19 pathogenesis via inhibition of virus replication and entry to its host cells.

The Iranian researchers in study titled “A pharmacology-based comprehensive review on medicinal plants and phytoactive constituents possibly effective in the management of COVID-19” and published in the journal Phytotherapy Research, concluded:

“The novel coronavirus disease has appeared in China and so far just Remdesivir approved for emergency COVID-19 treatment. To the aim of the study, the medicinal plants and bioactive components may be effective in the treatment and supportive therapy of COVID-19 is presented in three sections. Various valuable medicinal plants with their bioactive components can interference with COVID-19 pathogenesis via inhibition of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) replication and entry to its host cells. Among those, Citrus Spp., C. sinensis (orange), and Glycyrrhiza glabra (licorice) are the most desirable herbal drink or fruit that can introduce as effective adjutant components in COVID-19 treat.

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“Also, some herbal medicines such as Andrographis paniculata (creat or green chiretta), Citrus spp. (citrus fruits such as orange, lime, lemon, grapefruit), and Cuminum cyminum (cumin) can alleviate fever and cough as the most common complication of COVID-19 via their anti-inflammatory effect. On the other hand, numerous medicinal plants such as Glycyrrhiza glabra, Thymus vulgaris (thyme), Allium sativum (garlic), Althea officinalis (marsh-mallow), and Panax ginseng (ginseng) may become effective in the prevention and supportive therapy of COVID-19 via modulating the immune system. In this review, we gathered possible useful medicinal plants and bioactive components in COVID-19 prevention and treatment to light a new scope for design further in-vivo and clinical studies.”

The researchers noted that, till now, no reliable plant-based clinical trial has been done on COVID-19. They noted: “As the importance of clinical data in plant selection for design further studies, several mentioned plants in this article, evaluated in clinical trials on the common cold and respiratory disorders, were gathered in this section.

The safety and efficacy of a specific C. sinensis formulation confirmed via a randomised, double blind, placebo-controlled study on healthy adults (18– 70 years old). The symptoms, illnesses duration, and symptoms day were fewer in subjects receiving C. sinensis formulation twice a day for three months in compression with participation in the placebo group. Also, this study showed the C. sinensis enhances gamma-interferon T cell function.

“The positive effect of A. paniculata on symptomatic treatment of uncomplicated upper respiratory tract infection confirmed via a systematic review of randomized controlled trials. Based on this review, A. paniculata extract can reduce symptom severity and introduce as a suitable alternative for uncomplicated acute respiratory tract infection. A double blind, randomised clinical trial was conducted on forty-six patients (seven-12 years old) who have intermittent asthma. The subjects were daily receiving the herbal mixture (50 g of M. chamomilla, 100 g of A. officinalis flower, 100 g of M. sylvestris flower, 100 g of Hyssopus officinalis floral branches, 50 g of Adiantum capillus-veneris aerial parts, 50 g of G. glabra roots, and 50 g of Ziziphus jujube fruit) or placebo randomly for five days. The result showed a significant reduction in cough severity and nighttime awakening in patients taking herbal mixture compared to those receiving placebo.

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“The efficacy and safety of cough (EMA) granules (1 g of A. officinalis, 100 mg of Sisymbrium irio, and 70 mg of Hedera helix powdered extract) were evaluated in the clinical trial on 150 patients (three to above 15 years old) for upper respiratory disorders. The subjects took cough (EMA) granules or placebo three times a day for one week. This study showed cough (EMA) granules possess positive effects in cough, cold, and flu symptoms and it was safe.”

Also, researchers at the Nigerian Institute for Pharmaceutical Research and Development (NIPRD) have discovered NIPRIMUNE, an immune-modulatory phytomedicine, from the plant Andrographis paniculata.

Although the Federal Ministry of Health has refused to invest in clinical trials of the plant since it proved effective against COVID-19, it is on record that Thailand in January 2021 approved Andrographis paniculata for the management of COVID-19 infection. Also, Andrographis paniculata is one of the basic ingredients in Prof. Maurice Iwu’s COVID-19 formulation that is presently going through clinical trials.

Previous studies had shown that A. paniculata is one of the plants used for treating febrile illnesses possibly due to malarial and bacterial infections in local communities in Nigeria. It is locally called Jogbo because of its bitterness but popularly called Mejemeje (seven-seven) among Yoruba speaking natives in Nigeria because an average dosage comprises seven leaves eaten raw once or twice daily for about five days in the treatment of febrile illness or chronic debility and some herbalist also recommend it for treatment of hypertension.

Meanwhile, other studies have shown that plant extracts containing different secondary metabolites possess various medicinal properties, such as antimicrobial and antispasmodic activity, with minimal side effects. For example, thyme was once used for the treatment of asthma, laryngitis, the common cold, and throat congestion. During the sixteenth and seventeenth centuries, wild thyme was used for the treatment of malaria and epilepsy. The Balkans also used thyme as anti-cholesterolemic and immuno-stimulant.

Another interesting immuno-modulatory property of thymol is that it can enhance the expression of CD4, CD8, and Th1 cytokines through upregulation of interferon 4 (IFN-4) expression. This agent can also boost the secretion of interleukin-12 (IL-12).

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Emodin is another phytocompound that acts as an inhibitor of the 3a ion channel of SARS-CoV and HCoV-OC43 coronaviruses. Previous studies have also revealed that high concentrations of emodin can inhibit different stages of the virus life cycle.

Considering the antiviral activity of medicinal herbs, a new study published in the journal Current Pharmacology Reports focuses on the identification of potent phytochemicals from Himalayan herbs, namely, Rheum emodi, Thymus serpyllum, and Artemisia annua, for the treatment of COVID-19.

Herein, an in silico approach demonstrated the potential of unique phytocompounds (emodin, thymol, and carvacrol) to bind SARS-CoV-2 S glycoproteins (6VXX and 6VYB), the B.1.351 variant’s S glycoprotein, and also with ACE2. These phytocompounds could also prevent the binding of SARS-CoV-2 to the host’s ACE2, TMPRSS2, and neutrapilin-1 receptors.

Chloroquine has previously been used for the treatment of COVID-19. Owing to this, the authors compared the binding pattern of chloroquine and artemisinin with S proteins (6VXX, 6VYB) and its variant 7NXA, to understand its mode of action and inhibitory effects.

In this study, researchers used the AutoDock/Vina software to identify phytochemicals that can bind with the S protein. These molecular docking studies screened numerous phytocompounds and narrowed them down to emodin, which showed the best binding affinity with 6VYB and SARS-CoV-2 B.1.351 variant (7NXA). Emodin also showed the best interactions with TMPRSS 2 and ACE2.

Interactions between targeted protein receptor SARS-CoV-2 spike glycoprotein (PDB ID: 6VXX) with artemisinin (A) and emodin (B) using Chimera.

In this study, although the lowest binding energy was observed in artemisinin with 6VXX and 6VYB, this compound showed significant interaction with TMPRSS 2 and ACE2. Molecular dynamics (MD) simulation was also performed for 50ns. In the Ramachandran plot developed after MD, both the S-protein domains showed less than 1.0 per cent outlier amino acid residues.

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Taken together, the MD simulation study revealed that the interaction of artemisinin with 6VYB as compared to 6VXX was more stable. The researchers also found that all phytocompounds that were evaluated in this study are non-toxic and non-carcinogenic.

They concluded: “Considering these results, the authors recommend artemisinin as a potential phytocompound that can effectively inhibit the interaction between SARS-CoV-2 and ACE-2 receptor, especially when the S protein is in an open state conformation.

“The current research is unique because it has compared the open (6YVB) and closed (6VXX) conformations of S proteins. Interestingly, the open state of the S protein (6YVB), which was found to be more pathogenic, showed more stable interaction with artemisinin as compared to the closed state (6VXX).

“Future in vitro and in vivo studies will need to be conducted to determine the therapeutic efficacy of artemisinin for the treatment of COVID-19.”

Also, researchers say they have added to evidence that the compound farnesol, found naturally in herbs, and berries and other fruits, prevents and reverses brain damage linked to Parkinson’s disease in mouse studies.

Johns Hopkins Medicine researchers say they have added to evidence that the compound farnesol, found naturally in herbs, and berries and other fruits, prevents and reverses brain damage linked to Parkinson’s disease in mouse studies.

The compound, used in flavorings and perfume-making, can prevent the loss of neurons that produce dopamine in the brains of mice by deactivating PARIS, a key protein involved in the disease’s progression. Loss of such neurons affects movement and cognition, leading to hallmark symptoms of Parkinson’s disease such as tremors, muscle rigidity, confusion and dementia. Farnesol’s ability to block PARIS, say the researchers, could guide development of new Parkinson’s disease interventions that specifically target this protein.

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“Our experiments showed that farnesol both significantly prevented the loss of dopamine neurons and reversed behavioral deficits in mice, indicating its promise as a potential drug treatment to prevent Parkinson’s disease,” says Dr. Ted Dawson, director of the Johns Hopkins Institute for Cell Engineering and professor of neurology at the Johns Hopkins University School of Medicine.

Results of the new study, published July 28, in Science Translational Medicine, detail how the researchers identified farnesol’s potential by screening a large library of drugs to find those that inhibited PARIS.

In the brains of people with Parkinson’s disease, a buildup of PARIS slows down the manufacture of the protective protein PGC-1alpha. The protein shields brain cells from damaging reactive oxygen molecules that accumulate in the brain. Without PGC-1alpha, dopamine neurons die off, leading to the cognitive and physical changes associated with Parkinson’s disease.

To study whether farnesol could protect brains from the effects of PARIS accumulation, the researchers fed mice either a farnesol-supplemented diet or a regular mouse diet for one week. Then, the researchers administered pre-formed fibrils of the protein alpha-synuclein, which is associated with the effects of Parkinson’s disease in the brain.

The researchers found that the mice fed the farnesol diet performed better on a strength and coordination test designed to detect advancement of Parkinson’s disease symptoms. On average, the mice performed 100 per cent better than mice injected with alpha-synuclein, but fed a regular diet.

When the researchers later studied brain tissue of mice in the two groups, they found that the mice fed a farnesol-supplemented diet had twice as many healthy dopamine neurons than mice not fed the farnesol-enriched diet. The farnesol-fed mice also had approximately 55 per cent more of the protective protein PGC-1alpha in their brains than the untreated mice.

In chemical experiments, the researchers confirmed that farnesol binds to PARIS, changing the protein’s shape so that it can no longer interfere with PGC-1alpha production.

While farnesol is naturally produced, synthetic versions are used in commerce, and the amounts people get through diet is unclear. The researchers caution that safe doses of farnesol for humans have not yet been determined, and that only carefully controlled clinical trials can do so.

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Though more research is needed, Dawson and his team hope farnesol can someday be used to create treatments that prevent or reverse brain damage caused by Parkinson’s disease.

Meanwhile, healthy lifestyle factors such as abstinence from smoking and drinking, low body mass index, and exercise correlated with decreased cancer incidence, even in individuals with a high genetic risk.

The study titled “Genetic risk for overall cancer and the benefit of adherence to a healthy lifestyle” was published in the journal Cancer Research.

As genetic research continues to uncover loci, or areas in DNA, with specific changes that influence cancer risk, researchers can define polygenic risk scores (PRS) — personalized estimates of an individual’s cancer risk — based on a patient’s unique combination of these changes. However, most PRS are generated for a specific cancer type, rather than for overall cancer risk.

“A PRS indicating risk of a certain cancer is important but not enough,” Jin said. “We tried to create an indicator — the cancer polygenic risk score (CPRS) — to measure the genetic risk of cancer as a whole.”

Jin and colleagues calculated individual PRS for 16 cancers in men and 18 cancers in women, using available data from genome-wide association studies. They then used statistical methods to combine these scores into a single measure of cancer risk, based on the relative proportion of each cancer type in the general population. Separate CPRS were generated for men and women.

To validate their CPRS, the researchers utilized genotype information from 202,842 men and 239,659 women from the UK Biobank; a cohort of general-population participants recruited from England, Scotland, and Wales between 2006 and 2009, and calculated a CPRS for each individual.

UK Biobank participants were surveyed upon enrollment for various lifestyle factors, including smoking and alcohol consumption, body mass index, exercise habits, and typical diet. Based on these factors, Jin and colleagues classified each patient as having an unfavorable (zero to one healthy factors), intermediate (two to three healthy factors), or favorable (four to five healthy factors) overall lifestyle.

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Patients with the highest quintile CPRS were nearly twice as likely (for men) and 1.6 times as likely (for women) to have a cancer diagnosis by their most recent follow-up, in 2015 or 2016. Notably, 97 percent of patients in the study had a high genetic risk (top quintile) of at least one cancer type. “This suggests that almost everyone is susceptible to at least one type of cancer,” Jin said. “It further indicates the importance of adherence to a healthy lifestyle for everyone.”

Patients with an unfavorable lifestyle and the highest quintile genetic risk were 2.99 times (in men) and 2.38 times (in women) more likely to develop cancer than those with a favorable lifestyle and the lowest quintile of genetic risk.

Among patients with high genetic risk, the five-year cancer incidence was 7.23 percent in men and 5.77 percent in women with an unfavorable lifestyle, compared with 5.51 percent in men and 3.69 percent in women with a favorable lifestyle. The decreased percentages are comparable to the cancer risk in individuals with intermediate genetic risk, Jin said. Similar trends were observed in all genetic risk categories, suggesting that patients could benefit from a healthy lifestyle regardless of genetic risk.

Limitations of this study include the fact that only the strongest genetic risk loci were included in the individual PRS, which disregards the influence of loci with weaker effects. Researchers also noted an imbalance in the number of loci included between different cancer types, which can potentially skew their individual impact.

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