Beneficial Effects of Daily Consumption of Garlic and Onion Extract Concentrate on Infectious Respiratory Diseases in Elderly Resident Volunteers.

Aging is a biological process with high susceptibility to several infections. This risk increases in older patients in residential care facilities (RCF). Thus, there is a clear demand for developing preventive interventions with new therapeutic compounds that combine efficacy and safety. This could be the case of compounds derived from plants of the genus Allium spp. The purpose of this study was to evaluate the impact of a combination of a garlic and onion extract concentrate standardized in organosulfur compounds derived from propiin on the incidence of respiratory tract infections in elderly patients of RCF. Sixty-five volunteers were selected at random to receive a placebo or a single daily dose of the extract for thirty-six weeks. Different clinical visits were performed to evaluate the main respiratory diseases with an infectious origin, as well as the associated symptoms and their duration. The extract showed a clinical safety profile and significantly reduced the incidence of respiratory infections. Moreover, the treatment decreased the number and duration of the associated symptoms compared with the placebo group. For the first time, we demonstrated the protective effect of Alliaceae extract in respiratory infectious diseases in elderly healthy volunteers, which could be used prophylactically against the most common infectious respiratory diseases.

Adaptogens on Depression-Related Outcomes: A Systematic Integrative Review and Rationale of Synergism with Physical Activity.

Depression is considered the most important disorder affecting mental health. The aim of this systematic integrative review was: (i) to describe the effects of supplementation with adaptogens on variables related to depression in adults; and (ii) to discuss the potential combination with physical exercise to aid planning and commissioning future clinical research. An integrative review was developed complementing the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PROSPERO registration: CRD42021249682). A total of 41 articles met the inclusion criteria. With a Price index of 46.4%, we found that: (i) Hypericum perforatum (St. John's Wort) is the most studied and supported adaptogen (17/41 [41.46%], three systematic reviews with meta-analysis) followed by Crocus sativus L. or saffron (6/41 [14.63%], three systematic reviews with meta-analysis and two systematic reviews); (ii) it is possible that the significantly better performance of adaptogens over placebo is due to the reduction of allostatic load via the action of secondary metabolites on BDNF regulation; and, (iii) the number of studies reporting physical activity levels is limited or null for those that combine an exercise program with the consumption of adaptogens. Aware of the need for a multidisciplinary approach for depression treatment, this systematic integrative review provides an up-to-date view for supporting the use of St. John's Wort and saffron as non-pharmacological strategies while also help commissioning future research on the efficacy of other adaptogens. It also contributes to the design of future clinical research studies that evaluate the consumption of herbal extracts plus physical exercise, mainly resistance training, as a potentially safe and powerful strategy to treat depression.

Pharmacological potential of Withania somnifera (L.) Dunal and Tinospora cordifolia (Willd.) Miers on the experimental models of COVID-19, T cell differentiation, and neutrophil functions.

Cytokine release syndrome (CRS) due to severe acute respiratory coronavirus-2 (SARS-CoV-2) infection leads to life-threatening pneumonia which has been associated with coronavirus disease (COVID-19) pathologies. Centuries-old Asian traditional medicines such as Withania somnifera (L.) Dunal (WS) and Tinospora cordifolia (Willd.) Miers (TC) possess potent immunomodulatory effects and were used by the AYUSH ministry, in India during the COVID-19 pandemic. In the present study, we investigated WS and TC's anti-viral and immunomodulatory efficacy at the human equivalent doses using suitable in vitro and in vivo models. While both WS and TC showed immuno-modulatory potential, WS showed robust protection against loss in body weight, viral load, and pulmonary pathology in the hamster model of SARS-CoV2. In vitro pretreatment of mice and human neutrophils with WS and TC had no adverse effect on PMA, calcium ionophore, and TRLM-induced ROS generation, phagocytosis, bactericidal activity, and NETs formation. Interestingly, WS significantly suppressed the pro-inflammatory cytokines-induced Th1, Th2, and Th17 differentiation. We also used hACE2 transgenic mice to further investigate the efficacy of WS against acute SARS-CoV2 infection. Prophylactic treatment of WS in the hACE2 mice model showed significant protection against body weight loss, inflammation, and the lung viral load. The results obtained indicate that WS promoted the immunosuppressive environment in the hamster and hACE2 transgenic mice models and limited the worsening of the disease by reducing inflammation, suggesting that WS might be useful against other acute viral infections. The present study thus provides pre-clinical efficacy data to demonstrate a robust protective effect of WS against COVID-19 through its broader immunomodulatory activity.

Current Insights on Bioactive Molecules, Antioxidant, Anti-Inflammatory, and Other Pharmacological Activities of Cinnamomum camphora Linn.

C. camphora is a renowned traditional Unani medicinal herb and belongs to the family Lauraceae. It has therapeutic applications in various ailments and prophylactic properties to prevent flu-like epidemic symptoms and COVID-19. This comprehensive appraisal is to familiarize the reader with the traditional, broad applications of camphor both in Unani and modern medicine and its effects on bioactive molecules. Electronic databases such as Web of Science, PubMed, Google Scholar, Scopus, and Research Gate were searched for bioactive molecules, and preclinical/clinical research and including 59 research and review papers up to 2022 were retrieved. Additionally, 21 classical Unani and English herbal pharmacopeia books with ethnomedicinal properties and therapeutic applications were explored. Oxidative stress significantly impacts aging, obesity, diabetes mellitus, depression, and neurodegenerative diseases. The polyphenolic bioactive compounds such as linalool, borneol, and nerolidol of C. camphora have antioxidant activity and have the potential to remove free radicals. Its other major bioactive molecules are camphor, cineole, limelol, safrole, limonene, alpha-pinene, and cineole with anti-inflammatory, antibacterial, anxiolytic, analgesic, immunomodulatory, antihyperlipidemic, and many other pharmacological properties have been established in vitro or in vivo preclinical research. Natural bioactive molecules and their mechanisms of action and applications in diseases have been highlighted, with future prospects, gaps, and priorities that need to be addressed.

Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial.

INTRODUCTION: Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS: Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS: A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS: Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

Therapeutic Application, Phytoactives and Pharmacology of Tinospora cordifolia: An Evocative Review.

Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.

Ginger for Healthy Ageing: A Systematic Review on Current Evidence of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties.

The world's population is ageing at an accelerated pace. Ageing is a natural, physiological but highly complex and multifactorial process that all species in the Tree of Life experience over time. Physical and mental disabilities, and age-related diseases, would increase along with the increasing life expectancy. Ginger (Zingiber officinale) is a plant that belongs to the Zingiberaceae family, native to Southeast Asia. For hundreds of years, ginger has been consumed in various ways by the natives of Asian countries, both as culinary and medicinal herb for the treatment of many diseases. Mounting evidence suggests that ginger can promote healthy ageing, reduce morbidity, and prolong healthy lifespan. Ginger, a well-known natural product, has been demonstrated to possess antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as an outstanding antiviral activity due to a high concentration of antiviral compounds. In this review, the current evidence on the potential role of ginger and its active compounds in the prevention of ageing is discussed.

Anti-inflammatory and antioxidant activities of Gymnema Sylvestre extract rescue acute respiratory distress syndrome in rats via modulating the NF-κB/MAPK pathway.

Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality in COVID-19 patients, due to limited therapeutic options. This prompted us to explore natural sources to mitigate this condition. Gymnema Sylvestre (GS) is an ancient medicinal plant known to have various therapeutic effects. This investigation examined the therapeutic effect of hydroalcoholic extract of Gymnema Sylvestre (HAEGS) against lipopolysaccharide (LPS)-induced lung injury and ARDS in in vitro and in vivo models. UHPLC-HRMS/GC-MS was employed for characterizing the HAEGS and identified several active derivatives including gymnemic acid, gymnemasaponins, gymnemoside, gymnemasin, quercetin, and long fatty acids. Gene expression by RT-qPCR and DCFDA analysis by flow cytometry revealed that several inflammatory cytokine/chemokine, cell injury markers, and reactive oxygen species (ROS) levels were highly upregulated in LPS control and were significantly reduced upon HAEGS treatment. Consistent with the in vitro studies, we found that in LPS-induced ARDS model, pre-treatment with HAEGS significantly suppressed the LPS-induced elevation of inflammatory cell infiltrations, cytokine/chemokine marker expression, ROS levels, and lung injury in a dose-dependent manner. Further mechanistic studies demonstrated that HAEGS suppressed oxidative stress by modulating the NRF2 pathway and ameliorated the ARDS through the NF-κB/MAPK signalling pathway. Additional fractionation results revealed that fraction 6 which has the exclusive composition of gymnemic acid derivatives showed better anti-inflammatory effects (inhibition of IL-6 and IL-1ß) at lower concentrations compared to HAEGS. Overall, HAEGS significantly mitigated LPS-induced lung injury and ARDS by targeting the NF-κB/MAPK signalling pathway. Thus, our work unravels the protective role of HAEGS for the first time in managing ARDS.

Citrus junos Tanaka Peel Extract Ameliorates HDM-Induced Lung Inflammation and Immune Responses In Vivo.

In the wake of the COVID-19 pandemic, lung disorders have become a major health concern for humans. Allergic asthma is the most prevalent form of asthma, and its treatments target the inflammation process. Despite significant developments in the diagnosis and management of allergic asthma, side effects are a major concern. Additionally, its extreme heterogeneity impedes the efficacy of the majority of treatments. Thus, newer, safer therapeutic substances, such as natural products, are desired. Citrus junos Tanaka has traditionally been utilized as an anti-inflammatory, sedative, antipyretic, and antitoxic substance. In this study, the protective effects of Citrus junos Tanaka peel extract (B215) against lung inflammation were examined, and efforts were made to understand the underlying protective mechanism using an HDM-induced lung inflammation murine model. The administration of B215 reduced immune cell infiltration in the lungs, plasma IgE levels, airway resistance, mucus hypersecretions, and cytokine production. These favorable effects alleviated HDM-induced lung inflammation by modulating the NF-κB signaling pathway. Hence, B215 might be a promising functional food to treat lung inflammation without adverse effects.

Screening and evaluation of cytotoxicity and antiviral effects of secondary metabolites from water extracts of Bersama abyssinica against SARS-CoV-2 Delta.

BACKGROUND: Bersama abyssinica is a common herb in Africa, with diverse medical uses in different areas. The plant is well-known in Tanzania for treating respiratory disorders such as TB, tonsillitis, bronchitis, and asthma, and it has lately been utilized to treat COVID-19 symptoms. Water extract of leaf and stem bark has been registered as an herbal medication known as 'Coviba Dawa' in Tanzania for the relief of bacterial respiratory infections. The extracts, however, have not been scientifically tested for their anti-viral activities. The aim of this work was to test for the cytotoxicity and antiviral effects of bioactive ingredients from B. abyssinica extracts against the Delta variant of the SARS-CoV-2 coronavirus. METHODS: B. abyssinica leaves and stem bark were dried under shade in room temperature and then pulverized to obtain small pieces before soaking into different solvents. One hundred grams of each, leaves and stem bark, were extracted in petroleum ether, dichloromethane, ethyl acetate and methanol. Water extract was obtained by decoction of stem bark and leaves into water. Phenols, flavonoids, tannins, and antioxidants were confirmed as components of the extracts. Analysis of polar extracts of bark stem bark and leaves was done. Antiviral screening and cytotoxicity experiments were conducted in a Biosafety Level 3 (BSL-3) Laboratory facility according to International Standard Operating Procedures (SOPs). RESULTS: By the use of LC-MS/MS analysis, this study confirmed the existence of four phenolic compounds in B. abyssinica water extract; 2,4-di-tert-butylphenol, 4-formyl-2-methoxyphenyl propionate, 7,8-Dihydroxy-4-methylcoumarin, and 2,3, 6-trimethoxyflavone with antioxidant activity. This study showed that, while the water extracts of B. abyssinica had significant antiviral activity against SARS Cov2 virus, it showed no cytotoxicity effect on Vero E6 cells. In particular, the water extract (Coviba dawa) showed 75% while ethylacetate fraction of B. abyssinica leaves showed a 50% in vitro viral inhibition, indicating that these substances may be useful for the development of future anti-viral agents. CONCLUSION: We therefore recommend isolation of compounds for further profiling and development with a broader concentration range. We further recommend studies that determine the antiviral activity of extracts of B.abyssinica on other viral pathogens of clinical concern.

Alleviation of Post-COVID-19 Cognitive Deficits by Treatment with EGb 761®: A Case Series.

BACKGROUND Cognitive symptoms persisting longer than 3 months after infection, such as memory loss, or difficulties concentrating, have been reported in up to one-third of patients after COVID-19. Evidence-based therapeutic interventions to treat post-COVID-19 symptoms (also called "Long-COVID symptoms") have not yet been established, and the treating physicians must rely on conjecture to help patients. Based on its mechanism of action and its efficacy in treating cognitive impairment, as well as its good tolerability, the Ginkgo biloba special extract EGb 761 has been suggested as a remedy to alleviate cognitive post-COVID-19 symptoms. In many studies, EGb 761 has been demonstrated to protect endothelial cells, to have potent anti-inflammatory effects, and to enhance neuroplasticity. CASE REPORT Here, we report for the first time the application of EGb 761 in the therapy of post-COVID-19-related cognitive deficits. Three women and 2 men, aged 26 to 59 years (average age 34.6 years), presented with concentration and attention deficits, cognitive deficiencies, and/or fatigue 9-35 weeks after infection. A daily dose of 2×80 mg of EGb 761 did not cause any detectable adverse effects, and it substantially improved or completely restored cognitive deficits and, when initially present, also other symptoms, such as fatigue and hyposmia, within an observation period of up to 6 months. CONCLUSIONS Our observations support the hypothesis that EGb 761 might be a low-risk treatment option for post-COVID-19 patients with cognitive symptoms. Moreover, we derive recommendations for randomized controlled clinical trials to confirm efficacy in that indication.

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy.

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.

Plant Extracts as Add-On Therapeutics in Homeopathy: An Open-Label, Randomized Trial Using Mother Tinctures in Prediabetes.

Objectives: Prediabetes is a major public health concern. Different plant extracts are used in homeopathy as mother tinctures (MTs) for the treatment of prediabetes as an adjunct to individualized homeopathic medicines (IHMs); however, their effectiveness remains under-researched. Design: Open-label, randomized (1:1), active-controlled, pragmatic, exploratory trial. Setting: Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India. Subjects: Eighty-nine patients with prediabetes. Interventions: Group 1 (n = 45; IHMs plus any one of the following MTs: Cephalandra indica, Gymnema sylvestre, and Syzygium jambolanum; experimental/verum) versus Group 2 (n = 44; IHMs only; control). Outcome measures: Blood parameters, including-the fasting blood sugar (FBS) level, blood sugar level 2 h after ingestion of 75 g of glucose (oral glucose tolerance test [OGTT] result), and glycosylated hemoglobin percentage (HbA1c%), and symptoms, including the Diabetes Symptom Checklist-Revised (DSC-R) score; all of them were measured at baseline and after 3 and 6 months. Results: Although recruitment of 140 patients was initially planned, the target sample size could not be achieved because of coronavirus disease pandemic-related restrictions. Only 89 patients could be enrolled, and the trial had to be terminated prematurely owing to the time constraints of the project. The data of 82 patients (Group 1, n = 40; Group 2, n = 42) were analyzed using a modified intention-to-treat approach. Improvements in all outcomes were greater in Group 1 than in Group 2, but without a significant difference: FBS level (F1, 80 = 4.095, p = 0.046), OGTT result (F1, 80 = 2.399, p = 0.125), HbA1c% (F1, 80 = 1.612, p = 0.208), and DSC-R score (F1, 80 = 0.023, p = 0.880). Conclusions: A promising but nonsignificant trend favored the combination of MTs and IHMs compared with IHMs alone among the patients with prediabetes, especially in FBS. Therefore, further studies are required. Clinical Trial Registration Number: CTRI/2018/08/015319; secondary identifier (UTN): U1111-1218-6016.

Efficacy of Liriope platyphylla extract on improving respiratory function: A CONSORT-randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: The respiratory system is the first line of defense against outside pollutants. Recently, respiratory health has been receiving increasing attention due to the increase in fine dust, which reduces respiratory function and increases incidence of chronic obstructive pulmonary disease, and in coronavirus pandemic, which can cause severe acute respiratory syndrome. METHODS: This clinical pilot trial was designed to secure evidence for a main clinical trial and to confirm the efficacy and safety of Liriope platyphylla (LP) extract for improving respiratory function. We conducted a double-blind randomized placebo-controlled trial with 22 participants from June 30, 2021, to August 25, 2021. The primary outcome was Breathlessness, Cough, and Sputum Scale score. Secondary outcomes included forced vital capacity, forced expiratory volume at 1 second (FEV1), forced expiratory volume at 1 s/forced vital capacity ratio, cough assessment test score, chronic obstructive pulmonary disease assessment test score, peripheral blood mononuclear cell counts (white blood cells, eosinophils, T cells, and B cells), high-sensitivity C-reactive protein level, erythrocyte sedimentation rate, cytokine (interleukin-1ß, interleukin-4, tumor necrosis factor-α, interleukin-6, interleukin-8, interferon-γ, and immunoglobulin E) levels, antioxidant (glutathione peroxidase and superoxide dismutase) levels, and nitric oxide level. RESULTS: A total of 22 participants were randomly assigned to 2 groups: the LP group (n = 11), who took 1000 mg of LP extract per day, and the placebo group, who took 1000 mg of dextrin per day. Participants took 1 capsule twice a day for 4 weeks. For the Breathlessness, Cough, and Sputum Scale, the interaction between group and visit was statistically significant in a blend of analyses of variance. interleukin-8, tumor necrosis factor-α, and interferon-γ levels decreased more in the LP group than in the placebo group. The sample size required for large-scale clinical trials in the future was 50. There were no side effects. CONCLUSION: LP extract can enhance respiratory function. The detailed data we obtained support conducting the future main large-scale clinical trial.

Actional Mechanisms of Active Ingredients in Functional Food Adlay for Human Health.

Medicinal and food homologous adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional mechanism of functional ingredients in adlay to promote human health, based on the PubMed, CNKI, Google, and ISI Web of Science databases from 1988 to 2022. Adlay and its extracts are rich in 30 ingredients with more than 20 health effects based on human and animal or cell cultures: they are anti-cancer, anti-inflammation, anti-obesity, liver protective, anti-virus, gastroprotective, cardiovascular protective, anti-hypertension, heart disease preventive, melanogenesis inhibiting, anti-allergy, endocrine regulating, anti-diabetes, anti-cachexia, osteoporosis preventive, analgesic, neuroprotecting, suitable for the treatment of gout arthritis, life extending, anti-fungi, and detoxifying effects. Function components with anti-oxidants are rich in adlay. These results support the notion that adlay seeds may be one of the best functional foods and further reveal the action mechanism of six major functional ingredients (oils, polysaccharides, phenols, phytosterols, coixol, and resistant starch) for combating diseases. This review paper not only reveals the action mechanisms of adding adlay to the diet to overcome 17 human diseases, but also provides a scientific basis for the development of functional foods and drugs for the treatment of human diseases.

Impact of Drug Metabolism/Pharmacokinetics and its Relevance Considering Traditional Medicine-based Anti-COVID-19 Drug Research.

BACKGROUND: The representative anti-COVID-19 herbs, i.e., Poriacocos, Pogostemon, Prunus, and Glycyrrhiza plants, are commonly used in the prevention and treatment of COVID-19, a pandemic caused by SARSCoV- 2. Diverse medicinal compounds with favorable anti-COVID-19 activities are abundant in these plants, and their unique pharmacological/pharmacokinetic properties have been revealed. However, the current trends in Drug Metabolism/Pharmacokinetic (DMPK) investigations of anti-COVID-19 herbs have not been systematically summarized. METHODS: In this study, the latest awareness, as well as the perception gaps regarding DMPK attributes, in the anti- COVID-19 drug development and clinical usage was critically examined and discussed. RESULTS: The extracts and compounds of P.cocos, Pogostemon, Prunus, and Glycyrrhiza plants show distinct and diverse absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties. The complicated herbherb interactions (HHIs) and herb-drug interactions (HDIs) of anti-COVID-19 Traditional Chinese Medicine (TCM) herb pair/formula dramatically influence the PK/pharmacodynamic (PD) performance of compounds thereof, which may inspire researchers to design innovative herbal/compound formulas for optimizing the therapeutic outcome of COVID-19 and related epidemic diseases. The ADME/T of some abundant compounds in anti-COVID-19 plants have been elucidated, but DMPK studies should be extended to more compounds of different medicinal parts, species, and formulations and would be facilitated by various omics platforms and computational analyses. CONCLUSION: In the framework of pharmacology and pharmacophylogeny, the DMPK knowledge base would promote the translation of bench findings into the clinical practice of anti-COVID-19 and speed up the anti-COVID-19 drug discovery and development.

Antiviral activity of medicinal plant-derived products against SARS-CoV-2.

This review presents information from several studies that have demonstrated the antiviral activity of extracts (Andrographis paniculata, Artemisia annua, Artemisia afra, Cannabis sativa, Curcuma longa, Echinacea purpurea, Olea europaea, Piper nigrum, and Punica granatum) and phytocompounds derived from medicinal plants (artemisinins, glycyrrhizin, and phenolic compounds) against SARS-CoV-2. A brief background of the plant products studied, the methodology used to evaluate the antiviral activity, the main findings from the research, and the possible mechanisms of action are presented. These plant products have been shown to impede the adsorption of SARS-CoV-2 to the host cell, and prevent multiplication of the virus post its entry into the host cell. In addition to antiviral activity, the plant products have also been demonstrated to exert an immunomodulatory effect by controlling the excessive release of cytokines, which is commonly associated with SARS-CoV-2 infections.

Prospects of Coffee Leaf against SARS-CoV-2 Infection.

In the current climate, many countries are in dire need of effective preventive methods to curb the Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) pandemic. The purpose of this research is to screen and explore natural plant extracts that have the potential to against SARS-CoV-2 and provide alternative options for SARS-CoV-2 prevention and hand sanitizer or spray-like disinfectants. We first used Spike-ACE2 ELISA and TMPRSS2 fluorescence resonance energy transfer (FRET) assays to screen extracts from agricultural by-products from Taiwan with the potential to impede SARS-CoV-2 infection. Next, the SARS-CoV-2 pseudo-particles (Vpp) infection assay was tested to validate the effectiveness. We identified an extract from coffee leaf (Coffea Arabica), a natural plant that effectively inhibited wild-type SARS-CoV-2, and five Variants of Concern (Alpha, Beta, Gamma, Delta, and Omicron strain) from entering host cells. In an attempt to apply coffee leaf extract for hand sanitizer or spray-like disinfectants, we designed a skin-like gelatin membrane experiment. We showed that the high concentration of coffee leaf extract on the skin surface could block SARS-CoV-2 into cells more potently than 75% Ethanol, a standard disinfectant to inactivate SARS-CoV-2. Finally, LC-HRMS analysis was used to identify compounds such as caffeine, chlorogenic acid (CGA), quinic acid, and mangiferin that are associated with an anti-SARS-CoV-2 activity. Our results demonstrated that coffee leaf extract, an agricultural by-product effectively inhibits SARS-CoV-2 Vpp infection through an ACE2-dependent mechanism and may be utilized to develop products against SARS-CoV-2 infection.

Medicinal uses, pharmacological activities, phytochemistry, and the molecular mechanisms of Punica granatum L. (pomegranate) plant extracts: A review.

Punica granatum L (pomegranate) is one of the Mediterranean medicinal plants that has been used for generations in treating ulcers, diarrhea, and male infertility. Increasing evidence has revealed that pomegranate possesses myriads of pharmacological activities such as anti-diabetic, anti-tumor, anti-inflammatory, anti-malaria, anti-fibrotic, anti-fungal, anti-bacterial, and other effects. Consumption of pomegranate could be used to improve gut microbiota, and therefore prevent obesity and diabetes. The mechanisms of actions of pomegranate, mainly involve nuclear factor-erythroid factor 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and mitogen-activated protein kinase (MAPK) signaling pathways. In recent times, in silico molecular docking studies demonstrated that pomegranate extract and or its phytochemicals are potential inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) spike protein and angiotensin-converting enzyme 2 (ACE2) receptor contact. Also, some clinical trials have indicated that pomegranate can be consumed for alleviation of non-alcoholic fatty liver disease, metabolic syndrome, dental infections, and menopausal symptoms. To date, active compounds, viz. alkaloids, anthocyanidins, tannins, flavonoids, phenolics, proanthocyanidins, sterols, terpenes, terpenoids, xanthonoids, fatty acids, organic acids, lignans, saccharides, and vitamin C have been isolated from pomegranate. Therefore, the current review article aimed to gather and presents an update on the ethnomedicinal uses, pharmacological activities, phytochemistry, and molecular mechanisms of Punica granatum L. This knowledge is of paramount importance in the future in drug discovery for the development of novel natural drugs for the treatment of various ailments.

A Comprehensive Review of Andrographis paniculata (Burm. f.) Nees and Its Constituents as Potential Lead Compounds for COVID-19 Drug Discovery.

The COVID-19 pandemic has intensively disrupted global health, economics, and well-being. Andrographis paniculata (Burm. f.) Nees has been used as a complementary treatment for COVID-19 in several Asian countries. This review aimed to summarize the information available regarding A. paniculata and its constituents, to provide critical points relating to its pharmacological properties, safety, and efficacy, revealing its potential to serve as a source of lead compounds for COVID-19 drug discovery. A. paniculata and its active compounds possess favorable antiviral, anti-inflammatory, immunomodulatory, and antipyretic activities that could be beneficial for COVID-19 treatment. Interestingly, recent in silico and in vitro studies have revealed that the active ingredients in A. paniculata showed promising activities against 3CLpro and its virus-specific target protein, human hACE2 protein; they also inhibit infectious virion production. Moreover, existing publications regarding randomized controlled trials demonstrated that the use of A. paniculata alone or in combination was superior to the placebo in reducing the severity of upper respiratory tract infection (URTI) manifestations, especially as part of early treatment, without serious side effects. Taken together, its chemical and biological properties, especially its antiviral activities against SARS-CoV-2, clinical trials on URTI, and the safety of A. paniculata, as discussed in this review, support the argument that A. paniculata is a promising natural source for drug discovery regarding COVID-19 post-infectious treatment, rather than prophylaxis.