Diabetic Nephropathy (DN) affects over half of the diabetic population, is a significant global health concern and a leading cause of end-stage renal disease (ESRD). Recent studies emphasised the potential of herbal medicinal plants, particularly those with antioxidant properties and anti-inflammatory properties, in treating DN. This research examines the active phytochemicals and molecular mechanisms of D5 chooranam in the treatment of DN. Data on these phytochemicals were sourced from the IMPPAT database. Sixteen compounds were selected for further analysis based on ADMET profiling criteria. Target prediction analysis was performed for the selected phytochemicals. Disease-associated targets were identified using multiple databases, and comparison of the phytochemical and disease target datasets revealed 462 overlapping targets. Functional analysis revealed enrichment in pathways related to insulin resistance, PI3K-AKT signaling, and AGE-RAGE metabolism. Hub targets were identified using degree measures, with the top 10 genes selected for further analysis. The compound kaempferol showed strong interactions with genes such as TP53, MAPK1, MAPK3, AKT1, and SRC. Molecular docking and 500 ns molecular dynamics simulation studies of these five complexes showed that the SRC–kaempferol complex exhibited stable interactions, structural stability throughout the simulation period, and favorable binding energies. This study elucidates the pharmacologically active compounds in D5 chooranam by combining traditional knowledge with modern scientific insights using network pharmacology, thereby informing treatment strategies.
Traditional medicine in India has a rich historical background with recognized systems such as Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa-Rigpa, and Homeopathy (Ayush). The Government of India has made significant efforts to promote these systems globally, with a focus on Yoga and Ayurveda. The establishment of the WHO Global Center for Traditional Medicine in India reflects the country’s growing leadership in this sector. Strengthened by scientific evidence on safety and efficacy, India has developed a robust regulatory framework covering education, research, and product development in Ayush systems. However, regulating traditional medicine in the 21st century remains challenging, as approximately 88% of countries use traditional and complementary medicine. This review highlights India’s initiatives in education, research, and regulatory mechanisms that support the advancement and global acceptance of Ayush systems.
Nipah virus (NiV) is a highly contagious zoonotic pathogen causing severe encephalitis and respiratory illnesses in humans. With a high fatality rate and no FDA-approved treatments, NiV poses a significant public health threat. This study conducts a comprehensive Bayesian phylogenetic analysis of all publicly available NiV genomes since the first human case. Additionally, a protein-protein interaction (PPI) network analysis focusing on Pteropus species was performed to identify potential therapeutic targets. High-throughput virtual screening assessed the inhibitory potential of Kabasura Kudineer Chooranam phytocompounds against these targets. Molecular dynamic simulations (MDS) were conducted to evaluate the stability and dynamic characteristics of NiV proteins bound to specific inhibitors. Bayesian phylogenetic analysis of 280 NiV genomes revealed two distinct clades among Indian isolates, highlighting significant regional diversity. Notably, the latest strain, OM135495, along with other NiV variants in Kerala, underscores the virus's rapid genetic evolution since 2015. The PPI network identified NiV-F, NiV-G, and NiV-N as key therapeutic targets. Among the tested phyto compounds, Vasicinone and Piperine exhibited strong binding affinities (-4.51 to -5.96 kcal/mol) and enhanced stability during MDS, suggesting their potential as antiviral agents. These findings indicate that phyto compounds may serve as viable alternatives for NiV treatment, paving the way for novel drug development. However, further validation through laboratory and animal studies is essential. This study enhances our understanding of NiV evolution, informs public health strategies, and contributes to preparedness for future outbreaks.
The present investigation provides a comprehensive analysis of the principal neuroactive phytochemicals and their molecular mechanisms of action in Bacopa monnieri, Centella asiatica, Curcuma longa, Mucuna pruriens, and Withania somnifera, all of which are traditionally recognized for their therapeutic potential in Alzheimer's disease. Phytochemical data were systematically retrieved from the IMPPAT database, followed by ADMET-based screening, which yielded 14 candidate compounds for further analysis. Target prediction for these compounds was performed using SwissTargetPrediction and the STITCH database, leading to the identification of four lead phytochemicals (Apigenin, Kaempferol, Genstein, and Rosmarinic acid) based on their predicted interaction networks. Disease-associated gene targets were extracted from the GEO and DisGeNET databases. Comparative mapping revealed 164 overlapping targets between the phytochemical and disease-associated gene sets, which were subjected to functional enrichment analysis to elucidate their biological relevance. Network topology analysis was employed to identify central nodes within the protein-protein interaction network, with the top five hub genes determined via betweenness centrality metrics. Molecular docking, followed by dynamics simulations, confirmed the strong binding affinity and conformational stability of apigenin and genistein with PTGS2, with docking scores of -8.07 kcal/mol and -7.59 kcal/mol, respectively. Additionally, the PTGS2-genistein interaction exhibited superior dynamics.
Background: Avaram Amrit, derived from a traditional medicinal plant, has shown potential in diabetes management. This study aimed to evaluate its clinical efficacy in glycemic control. Methods: A 12-week, open-label clinical trial was conducted with 9 type 2 diabetes patients. Participants received Avaram Amrit extract daily. Fasting and postprandial glucose levels were measured bi-weekly, with HbA1c assessed at baseline and week 12. Results: Fasting glucose levels decreased significantly from 252.54 ± 71.99 mg/dL at baseline to 195.50 ± 55.01 mg/dL at week 12 (p<0.001), representing a 22.6% reduction. Mean HbA1c decreased by 1.25 percentage points. Postprandial glucose levels showed consistent improvement across the study period. A strong positive correlation was observed between initial HbA1c and fasting glucose (r=0.89). Conclusion: Avaram Amrit demonstrated significant improvement in glycemic control over 12 weeks. The consistent decrease in both short-term (glucose levels) and long-term (HbA1c) measures indicates a positive response to the intervention. While promising, larger randomized controlled trials are necessary to confirm these findings and establish Avaram Amrit's role in diabetes management.
Ethnopharmacological relevance: Chikungunya disease (CHIKD) is caused by the alphavirus, chikungunya virus (CHIKV) and is characterized by acute fever and joint inflammation; the inflammation continues even after clearance of the virus from the system, persisting for several months to years. Currently, there are no modern medicines/vaccines available for its treatment and use of over-the-counter anti-inflammatory generic medicines to relieve symptoms is generally practiced. In India, Indian traditional medicines hold a lot of promise to treat this infection and are routinely used during outbreaks.Aim of the study: In the present study, we characterized the phytochemical and physicochemical properties of aqueous and ethanol extracts of the Vathasura Kudineer (VSK), a Andrographis based Siddha polyherbal formulation. Additionally, we evaluated its immunomodulatory and antiviral potential using an in vitro system. Materials and methods: Aqueous and ethanolic extracts of VSK were prepared and their physico and phyto-chemical properties were obtained by biochemical and biophysical assays, HPTLC and FTIR. The aqueous ex-tracts of VSK and several of its ingredients were evaluated for their cytotoxicity in Vero cells and using the maximum non-toxic concentration (MNTC), were processed further for evaluating their ability to inhibit CHIKV infection in Vero cells. We performed the co-treatment assay with ethanol extract of VSK and several of its in-gredients to assess the antiviral activity against chikungunya virus on Vero cells and through pre-treatment assay (anti-adhesive effect), co-incubation assay (virucidal effect) and post-treatment assay (post-entry effect) were evaluated. Further, we tested the aqueous extract of VSK along with some of its ingredients for their immuno-modulatory properties. We performed antioxidant and anti-inflammatory assays using LPS-simulated RAW 264.7 cells. For antioxidant capacity of extracts, we performed extra-cellular ABTS radical scavenging activity and intra-cellular effects on ROS generation and SOD activity. We assessed the effect on most important in-flammatory mediators like Nitric oxide (NO) and Prostaglandin E2 (PGE2) and pro-inflammatory cytokines like interleukin-1 beta (IL-113) and tumor necrosis factor alpha (TNF alpha).Results: We provided the fingerprint of the phytochemicals of both ethanol and aqueous extracts of VSK that can be used for identification. We observed that ethanol extract was able to inhibit CHIKV infection at MNTC with 48 h of treatment on Vero cells. Its ingredient VSKI-As (Anethum sowa) found to be most effective to show virucidal effect while VSKI-Cs (Clerodendrum serratum) and VSKI-Pn (Pipper nigrum) found to be effective in post-entry effect. VSK was able to show ABTS radical scavenging activity, reduce ROS generation, inhibit the inflamma-tory mediators (NO and PGE2) and pro-inflammatory cytokines (IL-113 and TNF alpha) production in LPS-stimulated RAW 264.7 cells.Conclusions: We provided the evidence that VSK has both immunomodulatory as well as antiviral potential. It shows virucidal as well as post-entry effects on chikungunya virus. VSK can inhibit pro-inflammatory cytokines, IL-113 and TNF alpha production by suppressing the inflammatory mediators, NO and PGE2.
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.
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.
Objectives: The purpose of this review article is focused on the photochemical constituents and therapeutic potential of Thulasi Ennai to combat pediatric bronchial asthma. Methods: The electronic databases such as Google Scholar, Medline/PubMed, Web of Science, Science Direct, Scopus and Directory of Open Access Journals (DOAJ), and reference lists have been looked to identify publications pertinent to the individual herbs of Thulasi Ennai. Results: The pharmacological effects of the herbs found in Thulasi Ennai possess anti-asthmatic, anti-inflammatory, antibacterial, antiviral, and other pharmacological effects relevant to the management of bronchial asthma. Conclusion: The present review concluded the safety of the Thulasi Ennai in preclinical studies. Further, clinical studies of Thulasi Ennai would need to be performed in humans to assess the efficacy of Thulasi Ennai.
In peripheral blood, cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which indicates molecular abnormalities in metastatic breast tumor tissue. The sequencing of cfDNA of Metastatic Breast Cancer (MBC) patients allows assessment of therapy response and noninvasive treatment. In the proposed study, clinically significant alterations in PIK3CA and TP53 genes associated with MBC resulting in a missense substitution of His1047Arg and Arg282Trp from an next-generation sequencing-based multi-gene panel were reported in a cfDNA of a patient with MBC. To investigate the impact of the reported mutation, we used molecular docking, molecular dynamics simulation, network analysis, and pathway analysis. Molecular Docking analysis determined the distinct binding pattern revealing H1047R-ATP complex has a higher number of Hydrogen bonds (H-bonds) and binding affinity with a slight difference compared to the PIK3CA-ATP complex. Following, molecular dynamics simulation for 200 ns, of which H1047R-ATP complex resulted in the instability of PIK3CA. Similarly, for TP53 mutant R282W, the zinc-free state (apo) and zinc-bounded (holo) complexes were investigated for conformational change between apo and holo complexes, of which the holo complex mutant R282W was unstable. To validate the conformational change of PIK3CA and TP53, 80% mutation of H1047R in the kinase domain of p110α expressed ubiquitously in PIK3CA protein that alters PI3K pathway, while R282W mutation in DNA binding helix (H2) region of P53 protein inhibits the transcription factor in P53 pathway causing MBC. According to our findings, the extrinsic (hypoxia, oxidative stress, and acidosis); intrinsic factors (MYC amplification) in PIK3CA and TP53 mutations will provide potential insights for developing novel therapeutic methods for MBC therapy.
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)-10-methyloctyl caffeate, (Z)-3-phenyl-2-propenal, 7-oxo-10 alpha-cucurbitadienol, and PLX-4720 collectively to be potential treatment agents for COVID-19.
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. In this study, we executed the molecular docking studies for Phytoconstituents of Siddha official formulation Kabasura Kudineer which is used in treating viral fever and respiratory diseases and a Novel Herbal Preparation - JACOM against the ongoing pandemic of novel coronavirus disease causative agent SARS-CoV-2 Spike protein. Further, we also conducted prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates using pkCSM and SwissADME web servers. Totally 37 compounds were screened, of these 9 compounds showed high binding efficiency. Based on these, we proposed the new formulation called as "SNACK –V".
Objective: COVID19 pandemic out of all odds has created an opportunity to offer treatment in an integrative manner. This study measures the Length of stay (LS) of patients in an integrative way, as done earlier in China and Vietnam. Length of stay, Clinical presentations, and Comorbidities were analyzed among COVID19 patients in ESI Hospital, Coimbatore, Tamil Nadu, India. Method: Retrospective cross-sectional data on 251 Positive COVID19 patients of both sexes irrespective of age admitted from 27 March 2020 and 26 April 2020 cases were included in the study. The final discharge date is taken as 5th May 2020. Kaplan Meier survival analysis was adopted. Results: Male, female ratio were 141(56.2%): 83(33.1%), 12 (4.8%) Male Child and 15 (6.0%) were Female child. 5.2% of the patients were in the age group greater than 60, 75.3% were in the age group 20-60, and the remaining 19.5% were 0- 20 age group. 84.9% of patients were Asymptomatic, while fever and cough were the main symptoms recorded in the remaining cases. CT scan was done for 7 patients. No mortality and no serious adverse events were reported. Comorbidity is 15% and does not influence hospital length of stay. The overall median length of stay is 12 days for those who were under ZVcKK (Median ST CI- 11.59-12.41). Conclusion: This study recorded a median of 12 days in the Length of stay and 13.5 days in the Length of stay average. Comparing earlier studies, patients taking ZVcKK have savings of 7 days. i.e., the relief speed is higher while using ZVcKK.
The SARS-CoV-2 was identified in December 2019 and spread quickly around the globe. Around 218 countries with 61,468,916 cases have been diagnosed as of November 27, 2020. The epidemic quarantine and symptomatic care plan control are the first step of the treatment in the absence of medicines and vaccines. The need for treatments/therapeutics is in high demand. Pharma companies are working around the clock to develop these treatments/therapeutics. Several traditional medicines are also followed as the treatments/therapeutics across the globe. In India, the traditional medicine system ranks to be one of the topmost promising treatments/therapeutics for ages. In COVID-19, the medicinal products for treatment, prophylaxis, and convalescence were listed based on the Siddha Medicine advisory provided by the Ministry of AYUSH. These drugs are recommended for the treatment and prophylaxis of symptoms. In reality, however, these medications have been in vogue for infectious diseases like Dengue and Chikungunya for the past two decades. In parallel, the in silico studies are positively helping in the drug discovery and unravel the drug mechanisms. The computational protein modeling techniques also play a significant role in identifying all the reference genome's proteins. This chapter discussed Siddha and Quarantine's traditional insight in viral diseases, Virus-based drug repurposing for coronaviruses, and various treatment, including significant drug repurposing and BSAA combination therapy. We have also used computational modeling techniques to identify and model the individual protein structures from the whole genome of SARS CoV-2. Finally, this chapter will explain the steps taken to develop and repurpose Kabasura Kudineer as a drug to inhibit the COVID-19 pandemic.
Due to erratic climate change, vector-borne diseases started flaring up from the second half of the last decade. Siddha medicine has been used as a public health tool to effectively manage chikungunya and dengue in the epidemics that happened in 2008 and 2016. Tamil Nadu government has made enormous efforts to control vector-borne diseases. Due to which morbidity and mortality due to vector borne diseases came down compared with other states. Two official Siddha formulations, namely Kabasura Kudineer Chooranam and Nilavembu Kudineer Chooranam and novel herbal formulation – JACOM, are used to combat vector-borne diseases. These decoctions lack an evidence base as a formulation. Screening has been done to check the efficacy of the formulation in inhibiting neuraminidase. Neuraminidase inhibition assay was performed to determine the activity of Siddha formulations. The Kabasura Kudineer Chooranam, Nilavembu Kudineer Chooranam and JACOM showed excellent inhibitory activity. The Kabasura Kudineer and Nilavembu Kudineer and JACOM aqueous extract showed maximum neuraminidase inhibition of 80.35%, 91.78% and 87.97%, respectively.
Siddha’s folk medicine system is used to enhance immune responses as preventive medicine Siddha medicine’s enormousplethora of data will enhance human wellbeing Since the oldyears, Kabasura Kudineer(KSK) has beenanimmunedrugtoseveralillnesses Aqueous extract was employed for preparing the extract and analyzed for Total Antioxidant Capacity, Fe2+ chelating activity assay, Hydrogen peroxide scavenging activity, ABTS Scavenging assay and Reducing power assay Thiswas found to possess high antioxidant properties of aqueous extract of KSK and their derivatives have been confirmed with the different tests This experimentation further affirms the antioxidative nature of KSK extract, which further aid in the fight in this COVID-19 pandemic situation
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 evidencebased 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 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. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Institute of Transdisciplinary Health Sciences and Technology and World Ayurveda Foundation.