In silico network pharmacology analysis and molecular docking validation of Swasa Kudori tablet for screening druggable phytoconstituents of asthma.

Traditional medicines are impactful in treating a cluster of respiratory-related illnesses. This paper demonstrates screening active, druggable phytoconstituents from a classical Siddha-based poly-herbal formulation called Swasa Kudori Tablet to treat asthma. The phytoconstituents of Swasa Kudori are identified as Calotropis gigantea, Piper nigrum, and (Co-drug) Abies webbiana. Active chemical compounds are extracted with the Chemical Entities of Biological Interest (ChEBI) database. The gene targets of each compound are identified based on the pharmacological activity using the DIGEP-Pred database. Thirty-two genes showing Pa> 0.7 is screened, and the target markers are selected after performing gene overlap evaluation with the asthma genes reported in GeneCards and DisGeNET database. Ten markers are identified, such as ADIPOQ, CASP8, CAT, CCL2, CD86, FKBP5, HMOX1, NFE2L2, TIMP1, VDR, in common, listed as molecular targets. Pharmacokinetic assessment (ADME) revealed five natural drug compounds 2-5-7-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one, (+)-catechin-3'-methyl ether, futoenone, 5-hydroxy-4',7-dimethoxyflavanone, and pinocembrin showing better druggability. Further screening delineates the target (HMOX1) and drug (pinocembrin) for molecular docking evaluation. When docked with HO-1, Pinocembrin showed a binding affinity of -8.0 kcal/mol. MD simulation studies substantiate the docking studies as HO-1 in complex with pinocembrin remains stable in the simulated trajectory. The current findings exhibit the significance of traditional medicines as potential drug candidates against asthma.

In silico network pharmacology study on Glycyrrhiza glabra: Analyzing the immune-boosting phytochemical properties of Siddha medicinal plant against COVID-19.

Immunosenescence is a pertinent factor in the mortality rate caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The changes in the immune system are strongly associated with age and provoke the deterioration of the individual's health. Traditional medical practices in ancient India effectively deal with COVID-19 by boosting natural immunity through medicinal plants. The anti-inflammatory and antiviral properties of Glycyrrhiza glabra are potent in fighting against COVID-19 and promote immunity boost against the severity of the infection. Athimadhura Chooranam, a polyherbal formulation containing Glycyrrhiza glabra as the main ingredient, is recommended as an antiviral Siddha herb by the Ministry of AYUSH. This paper is intended to identify the phytoconstituents of Glycyrrhiza glabra that are actively involved in preventing individuals from COVID-19 transmission. The modulated pathways, enrichment study, and drug-likeness are calculated from the target proteins of the phytoconstituents at the pharmacological activity (Pa) of more than 0.7. Liquiritigenin and Isoliquiritin, the natural compounds in Glycyrrhiza glabra, belong to the flavonoid class and exhibit ameliorative effects against COVID-19. The latter compound displays a higher protein interaction to a maximum of six, out of which HMOX1, PLAU, and PGR are top-hub genes. ADMET screening further confirms the significance of the abovementioned components containing better drug-likeness. The molecular docking and molecular dynamics method identified liquiritigenin as a possible lead molecule capable of inhibiting the activity of the major protease protein of SARS-CoV-2. The findings emphasize the importance of in silico network pharmacological assessments in delivering cost-effective, time-bound clinical drugs.

Understanding the activating mechanism of the immune system against COVID-19 by Traditional Indian Medicine: Network pharmacology approach.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly; it is raising the alarm around the globe. Though vaccines are currently available, the evolution and mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic. These drugs have been effective yet accommodating side effects, which also can be lethal. Complementary and alternative medicine is highly demanded since it embraces a holistic approach. Since ancient times, natural products have been used as drugs to treat various diseases in the medical field and are still widely practiced. Medicinal plants contain many active compounds that serve as the key to an effective drug design. The Kabasura kudineer and Nilavembu kudineer are the two most widely approved formulations to treat COVID-19. However, the mechanism of these formulations is not well known. The proposed study used a network pharmacology approach to understand the immune-boosting mechanism by the Kabasura kudineer, Nilavembu kudineer, and JACOM in treating COVID-19. The plants and phytochemical chemical compounds in the Kabasura kudineer, Nilavembu kudineer, and JACOM were obtained from the literature. The Swiss target prediction algorithm was used to predict the targets for these phytochemical compounds. The common genes for the COVID-19 infection and the drug targets were identified. The gene-gene interaction network was constructed to understand the interactions between these common genes and enrichment analyses to determine the biological process, molecular functions, cellular functions, pathways involved, etc. Finally, virtual screening and molecular docking studies were performed to identify the most potential targets and significant phytochemical compounds to treat the COVID-19. The present study identified potential targets as ACE, Cathepsin L, Cathepsin B, Cathepsin K, DPP4, EGFR, HDAC2, IL6, RIPK1, and VEGFA. Similarly, betulinic acid, 5″-(2⁗-Hydroxybenzyl) uvarinol, antofine, (S)-1'-methyloctyl caffeate, (Z)-3-phenyl-2-propenal, 7-oxo-10α-cucurbitadienol, and PLX-4720 collectively to be potential treatment agents for COVID-19.

In Silico computational screening of Kabasura Kudineer - Official Siddha Formulation and JACOM against SARS-CoV-2 spike protein.

BACKGROUND: Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds. OBJECTIVE: The study is aimed to execute the In Silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation - JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel corona virus disease SARS-CoV-2. METHOD: Cresset Flare software was used for molecular docking studies against the spike protein SARS-CoV-2 (PDB ID: 6VSB). Further, we also conducted insilico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers. RESULTS: Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-CoV-2 spike protein. All the phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as "SNACK-V" CONCLUSION: Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19.

Analysis of AYUSH studies registered in clinical trials registry of India from 2009 to 2020.

BACKGROUND: The Clinical Trials Registry-India (CTRI) is an initiative of the Indian Council of Medical Research, New Delhi, India (ICMR) and monitored by the ICMR-National Institute of Medical Statistics (NIMS) since July 20, 2007. Randomized clinical trials are considered as the gold standard in evidence-based medicine. Registration of clinical trials enables disseminating evidence among clinicians, researchers, and patients. It promotes transparency and avoids duplication. The registration process is mandatory for AYUSH clinical trials also. OBJECTIVES: This analysis is aimed to determine the different characteristics of registered AYUSH clinical trials in CTRI from 2009 to 2020. MATERIALS AND METHODS: A cross-sectional retrospective analysis was conducted. The information on registered clinical trials about AYUSH was obtained from the website www.ctri.nic.in from 2009 to 2020 (n = 3632; last accessed on July 30 2020). Data analysis considered the following factors for analysis using descriptive statistics. The number of clinical trials registered in AYUSH stream were classified according to registration type (retrospective/prospective), postgraduate dissertations (yes/no), primary sponsor, type of trial (interventional/observational), study design, health condition and State-wise distribution of sites of studies. RESULTS: The number of clinical trial registrations among AYUSH streams (3632) descends from Ayurveda (2054), followed by Siddha (635), Yoga (408), Unani (366) and Homoeopathy (169). Interventional studies dominate observational studies among all AYUSH registered trials. AYUSH streams took four years to register in CTRI due to an increase in reporting trials from 2013. Significant number of trials were registered retrospectively. The order of closure of retrospective registration has influenced an increase in prospective enrolment between 2017-2019. CONCLUSION: Registration of clinical trials in the CTRI should be encouraged. Randomized controlled trials (RCTs) occupy a rear seat which exposes an opportunity for trials and alarms about weak trials. Non-communicable diseases (NCDs) are registered more comparatively, which reflects the strength of AYUSH in NCDs. Most of the trials fall under phase 2, which seems to have an increasing opportunity for more trials. Certain visible flaws like registering Phase 2 trials as Phase 3 or 4 and domestic trials as international trials reflect human resources crunch in ICMR-CTRI in Issuing Certificates. These errors should be rectified by training the stakeholders effectively.

Antiviral activity of ethanolic extract of Nilavembu Kudineer against dengue and chikungunya virus through in vitro evaluation.

BACKGROUND: Currently, no vaccines or modern drugs are available for dengue and chikungunya and only symptomatic relief is provided to the patients. Siddha medicine, a traditional form of indigenous medical system uses specific polyherbal formulations for the treatment of such infections with considerable success. One such polyherbal formulation for the treatment of chikungunya and dengue is Nilavembu kudineer (NVK). The mechanistic details of this drug as an antiviral for chikungunya virus (CHIKV) and dengue virus (DENV) is poorly understood. OBJECTIVES: The current study was undertaken to study the efficacy of NVK as an antiviral formulation against CHIKV and DENV. MATERIALS AND METHODS: Cytotoxicity assays (MTT) were performed to determine the role of NVK as an antiviral during chikungunya and dengue infections in the following conditions-i). post infection, ii). during active infections and iii) protective, not allowing virus infection. RESULTS: It was observed that NVK provides protection against CHIKV and DENV-2 during active infection as well can help to prevent virus infection in the cells and it mainly depends on the cellular availability of drugs for maximum protection against both the infections. CONCLUSION: Our study establishes that extraction protocols are important to ensure maximum efficacy of NVK along with the time of addition of the drug during CHIKV and DENV infections in the cells. This study provides insights to the possible mode of action of NVK in in vitro condition during CHIKV and DENV infection.