Phytochemistry and Pharmacology of Indian Traditional Plant Hyssop (Hyssopus officinalis L.): A Review

Hyssopus officinalis is a traditional medicinal plant that belongs to the family Lamiaceae, which has been used for centuries for various purposes like carminative, expectorant, and cough reliever. It has been used for the treatment of numerous diseases in patients such as ulcers, asthma, jaundice, leprosy, dropsy, bronchitis, COPD, diabetes, AIDS, bacterial and fungal infections as an herbal remedy due to its fewer side effects and is more efficacies than other traditional medicine. Major classes of chemical compounds found in H. officinalis essential oil are bicyclic monoter-penes, monoterpenoids, acyclic monoterpenes, phenolic monoterpenoids, monocyclic monoterpenes, monocyclic sesquiterpenes, tricyclic sesquiterpenes, bicyclic sesquiterpenes, tricyclic sesquiterpe-noids, straight chain saturated hydrocarbons. Some of the major chemical constituents present in the H. officinalis are beta-pinene, alpha-pinene, 1, 8-cineole, apigenin, diosmin, caffeic acid, rosmarinic acid, cis-pinocamphone, trans-pinocamphone, iso-pinocamphone, pinocarvone, which are responsible for its various pharmacological activity. Various studies have been performed on the pharmacological activity of its extract, such as antioxidant, antimicrobial, anti-diabetic, anticancer, antiviral, anti-inflammatory, analgesic, anti-leishmanial, anthelmintic, anti-protozoal, and anti-anxiety. Recently, it is used as an anticancer agent and has been demonstrated by studying its cytotoxic and apoptotic effects on breast cancer and colon cancer cells. It is used as a potent antibacterial and antifungal agent being studied on the antibiotic-resistant bacterial and fungal strains recently, which can be further useful in developing herbal medicine against AMR. It is an excellent natural antioxidant due to the presence of polyphenolic compounds, and H. officinalis is used in various food industries as a source of natural antioxidants, which has minimum side effects as compared to artificial antioxi-dants. Furthermore, the pharmacological activity of these individual chemical constituents in H. officinalis extract still needs to be investigated for identifying the effectiveness of this plant in the natural treatment of various diseases. This review aims to collect various data regarding the traditional herbal plant hyssop (Hyssopus officinalis), including its photochemistry, chemical structures of the phyto-constituents and pharmacological profile, along with all the pharmacological models. This plant has significant importance in the health industry, so further studies are required on its effective usage against various emerging health problems, including COVID-19, cancer, diabetes, AMR.Copyright © 2023 Bentham Science Publishers.

Caffeic acid phenethyl ester: A review on its pharmacological importance, and its association with free radicals, COVID-19, and radiotherapy.

Caffeic acid phenethyl ester (CAPE), a main active component of propolis and a flavonoid, is one of the natural products that has attracted attention in recent years. CAPE, which has many properties such as anti-cancer, anti-inflammatory, antioxidant, antibacterial and anti-fungal, has shown many pharmacological potentials, including protective effects on multiple organs. Interestingly, molecular docking studies showed the possibility of binding of CAPE with replication enzyme. In addition, it was seen that in order to increase the binding security of the replication enzyme and CAPE, modifications can be made at three sites on the CAPE molecule, which leads to the possibility of the compound working more powerfully and usefully to prevent the proliferation of cancer cells and reduce its rate. Also, it was found that CAPE has an inhibitory effect against the main protease enzyme and may be effective in the treatment of SARS-CoV-2. This review covers in detail the importance of CAPE in alternative medicine, its pharmacological value, its potential as a cancer anti-proliferative agent, its dual role in radioprotection and radiosensitization, and its use against coronavirus disease 2019 (COVID-19).

The mint versus Covid hypothesis.

Recent lines of evidence suggest the intriguing hypothesis that consuming common culinary herbs of the mint family might help prevent or treat Covid. Individual citizens could easily explore the hypothesis using ordinary kitchen materials. I offer a philosophical framework to account for the puzzling lack of public health messaging about this interesting idea.

Antiviral and Anti-SARS-CoV-2 Activity of Natural Chlorogenic Acid and Its Synthetic Derivatives

Since the dawn of time, several viral epidemics have swept the globe, among them the current COVID-19 outbreak. The ongoing emergence and propagation of novel viral illnesses have compelled researchers to seek new therapeutic approaches that can get beyond the drawbacks of antivirals that are available right now. Medicinal plants have historically offered treatments for a range of illnesses. These bioactive compounds serve as the foundation for many "modern" pharmaceuticals. One of the essential polyphenols in various medicinal plants is Chlorogenic acid (CA), an ester of caffeic and quinic acid. Extensive research has revealed that CA possesses anti-inflammatory, anticarcinogenic, and antioxidant properties. This review aims to briefly summarise CA and its derivative's antiviral properties on various human viral diseases and their ability to fight the current COVID-19 disease. This review summarises CA antiviral action on the following viruses: influenza A virus (H1N1/H3N2/H7N9), hepatitis C virus (HCV) and hepatitis B virus (HBV), human immunodeficiency virus (HIV), infectious bronchitis virus (IBV), porcine reproductive and respiratory syndrome virus (PRRSV), herpes simplex virus (HSV)-1, enterovirus 71 (Ent 71), adenoviruses (AdenV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review will open the way for developing and designing potentially effective and broad-spectrum CA-based antiviral medicines.

In vitro antiviral effect of Mexican and Brazilian propolis and phenolic compounds against human coronavirus 229E.

Propolis is a resinous substance collected by bees (Apis mellifera). It is used for its biological properties. This natural product is available as a safe therapeutic option. Herein, we report the antiviral effects of brown propolis extract from Mexico and green and red propolis extracts from Brazil, as well as their phenolic compounds (quercetin, caffeic acid, and rutin) in preventing infection of MRC-5 cells by HCoV-229E. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. All samples studied showed antiviral activity. Green and brown propolis extracts, and quercetin exhibited the best EC50 values with values of 19.080, 11.240, and 77.208 µg/mL against HCoV-229E, respectively, and with TC50 of 62.19, 29.192, and 298 µg/mL on MRC-5 cells, respectively. These results are the first in vitro study of the effects of propolis on HCoV-229E and provide the basis for the development of natural formulations against other coronavirus strains.

Identification of Potential Inhibitors for Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) Angiotensin-converting Enzyme 2 and the Main Protease from Anatolian Traditional Plants

Background: The 2019 novel coronavirus disease (COVID-19) has caused a global health catastrophe by affecting the human population around the globe. Unfortunately, there is no specific medi-cation or treatment currently available for COVID-19. Objective: It is extremely important to find effective drug treatment in order to put an end to this pandemic period and return to normal daily life. In this context and considering the urgency, rather than focusing on the discovery of novel compounds, it is critical to explore the effects of existing herbal agents with proven antiviral properties on the virus. Methods: Molecular docking studies were carried out employing three different methods, Glide extra precision (XP) docking, induced fit docking (IFD), and molecular mechanics/generalized born surface area (MM/GBSA), to determine the potential antiviral and antibacterial effects of 58 phytochemicals present in Rosmarinus officinalis, Thymbra spicata, Satureja thymbra, and Stachys lavandulifolia plants against the main protease (Mpro) and angiotensin-converting enzyme 2 (ACE2) enzymes. Results: 7 compounds stood out among all the molecules, showing very high binding affinities. Accord-ing to our findings, the substances chlorogenic acid, rosmarinic acid, and rosmanol exhibited extremely significant binding affinities for both Mpro and ACE2 enzymes. Furthermore, carnosic acid and alpha-cadinol showed potent anti-Mpro activity, whereas caffeic acid and carvacrol exhibited promising anti-ACE2 activity. Conclusion: Chlorogenic acid, rosmarinic acid, rosmanol, carnosic acid, alpha-cadinol, caffeic acid, and carvacrol compounds have been shown to be powerful anti-SARS-CoV-2 agents in docking simulations against Mpro and ACE2 enzymes, as well as ADME investigations.

Clinical trials in times of pandemic: Adapting without losing quality (1/2). Embed a COVID-19 group in an ongoing trial

Introduction: The urgency of finding effective treatments for severe forms of COVID-19 has necessitated adaptations to clinical trial designs. Almost all of the initial randomized trials had to be open-label and placebo-free. We were able to seize the opportunity to conduct a double-blind placebo-controlled trial by integrating ourselves into an ongoing trial and offer here some lessons from this experience. Material and methods: The CAPE-COD trial (NCT 02517489) sought to show a decrease in day 28 mortality in patients admitted to critical care with community-acquired pneumonia and receiving hydrocortisone compared with placebo. The inclusion of patients with COVID-19 was possible but required urgent responses to several problems: i) choose between subgroup analysis or segregation of COVID patients from others;ii) simultaneously include in both trials or discontinue the parent trial;iii) adapt methods to achieve a rapid response, including changing the primary endpoint;iv) define the maximum size and stopping boundaries of a sequential trial in the absence of solid data on disease progression;v) quickly obtain ethical and regulatory approvals and funding;vi) conduct the trial in overcrowded centers;vii) not jeopardize the rigor of the parent trial despite an interruption in its recruitment [1]. These elements will be discussed orally. Results: 150 patients were included before the DSMB suggested that inclusions be stopped due to the pre-publication of RECOVERY. Hydrocortisone did not significantly reduce the primary endpoint, treatment failure (defined as death or persistent respiratory support) at day 21, but a post-hoc analysis showed that relative mortality at day 21 was 46% lower (14.7 vs. 27.4%) with hydrocortisone compared to placebo, a non-significant difference (p = 0.057) but with an effect size comparable to that observed in RECOVERY. Tolerance was good [2]. Discussion/Conclusion: The rapid response to many methodological problems allowed a trial with low risk of bias to be conducted despite the pandemic pressure.

Study on the potential of Sanghuangporus sanghuang and its components as COVID-19 spike protein receptor binding domain inhibitors.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has led to the most severe global pandemic, which began in Wuhan, China. Angiotensin-converting enzyme 2 (ACE2) combines with the spike protein of SARS-CoV-2, allowing the virus to cross the membrane and enter the cell. SARS-CoV-2 is modified by the transmembrane protease serine 2 (TMPRSS2) to facilitate access to cells. Accordingly, ACE2 and TMPRSS2 are targets of vital importance for the avoidance of SARS-CoV-2 infection. Sanghuangporus sanghuang (SS) is a traditional Chinese medicine that has been demonstrated to have antitumor, antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective and immunomodulatory properties. In this paper, we demonstrated that SS decreased ACE2 and TMPRSS2 expression in cell lines and a mouse model without cytotoxicity or organ damage. Liver and kidney sections were confirmed to have reduced expression of ACE2 and TMPRSS2 by immunohistochemistry (IHC) assessment. Then, hispidin, DBA, PAC, PAD and CA, phenolic compounds of SS, were also tested and verified to reduce the expression of ACE2 and TMPRSS2. In summary, the results indicate that SS and its phenolic compounds have latent capacity for preventing SARS-CoV-2 infection in the future.

Caffeic acid derivatives and polymethoxylated flavonoids from cat's whiskers (Orthosiphon stamineus) form stable complexes with SARS-CoV molecular targets: an in silico analysis

Cat's whiskers or the 'misai kucing' is an herbal plant native to the Southeast Asian region. The polyphenol enriched leaf extract contains numerous medicinal properties of major pharmaceutical interest. In this study, selected cat's whiskers polyphenols were screened computationally to predict the minimum binding affinities with severe acute respiratory syndrome coronavirus (SARS-CoV) molecular targets. Molecular docking analysis showed that the caffeic acid derivatives and polymethoxylated flavonoids from cat's whiskers bound stably to the binding pocket regions of SARS-CoV molecular targets at - 4.2 to - 7.1 kcal/mol. Furthermore, these cat's whiskers polyphenol-bound SARS-CoV complexes were held fairly strongly by hydrophobic interactions, hydrogen bonds, and electrostatic interactions at various extents.

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols.

The abundance of polyphenols in edible plants makes them an important component of human nutrition. Considering the ongoing COVID-19 pandemic, a number of studies have investigated polyphenols as bioactive constituents. We applied in-silico molecular docking as well as molecular dynamics supported by in-vitro assays to determine the inhibitory potential of various plant polyphenols against an important SARS-CoV-2 therapeutic target, the protease 3CLpro. Of the polyphenols in initial in-vitro screening, quercetin, ellagic acid, curcumin, epigallocatechin gallate and resveratrol showed IC50 values of 11.8 µM to 23.4 µM. In-silico molecular dynamics simulations indicated stable interactions with the 3CLpro active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used to measure the binding of polyphenols to 3CLpro in real time. Therefore, we provide evidence for inhibition of SARS-CoV-2 3CLpro by natural plant polyphenols, and suggest further research into the development of these novel 3CLpro inhibitors or biochemical probes.

Caffeic Acid on Metabolic Syndrome: A Review.

Metabolic syndrome (MetS) is a constellation of risk factors that may lead to a more sinister disease. Raised blood pressure, dyslipidemia in the form of elevated triglycerides and lowered high-density lipoprotein cholesterol, raised fasting glucose, and central obesity are the risk factors that could lead to full-blown diabetes, heart disease, and many others. With increasing sedentary lifestyles, coupled with the current COVID-19 pandemic, the numbers of people affected with MetS will be expected to grow in the coming years. While keeping these factors checked with the polypharmacy available currently, there is no single strategy that can halt or minimize the effect of MetS to patients. This opens the door for a more natural way of controlling the disease. Caffeic acid (CA) is a phytonutrient belonging to the flavonoids that can be found in abundance in plants, fruits, and vegetables. CA possesses a wide range of beneficial properties from antioxidant, immunomodulatory, antimicrobial, neuroprotective, antianxiolytic, antiproliferative, and anti-inflammatory activities. This review discusses the current discovery of the effect of CA against MetS.

Improvement of caffeic acid biotransformation into para-hydroxybenzoic acid by Candida albicans CI-24 via gamma irradiation and model-based optimization.

Para-hydroxybenzoic acid (PHBA) has great potential in biological applications due to its putative antiviral activity against SARS-CoV-2 and its antimicrobial activity in the face of the radically increasing number of multidrug-resistant pathogens. This is in addition to its antimutagenic, anti-inflammatory, antioxidant, hypoglycemic, antiestrogenic, and antiplatelet aggregating activities. In this study, an approximate sixfold increase in the production of PHBA was achieved via biotransformation of caffeic acid by Candida albicans. The improvement was performed in two steps: first, through mutation by gamma irradiation (5 KGy dose), resulting in the recovery of a mutant (CI-24), which produced approximately triple the amount of PHBA produced by the wild-type isolate. Then, biotransformation by this mutant was further optimized via response surface methodology model-based optimization. The maximum PHBA production (7.47 mg/mL) was obtained in a fermentation medium composed of 1% w/v yeast extract as a nitrogen source, with an initial pH of 6.6, incubated at 28 °C at an agitation rate of 250 rpm. To further enhance the performance and economics of the process, cells of the CI-24 mutant were immobilized in calcium alginate beads and could retain an equivalent biotransformation capacity after three successive biotransformation cycles.

Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19.

BACKGROUND: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. PURPOSE: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. METHODS: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. RESULTS: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. CONCLUSION: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.