Therapeutic and pharmacological efficacy of plant-derived bioactive compounds in targeting breast cancer.

Breast cancer (BC) ranks number one among cancers affecting women globally. Serious concerns include delayed diagnosis, poor prognosis, and adverse side effects of conventional treatment, leading to residual morbidity. Therefore, an alternative treatment approach that is safe and effective has become the need of the hour. In this regard, plant-based medicines via a combination of conventional drugs are gaining increasing acceptance worldwide, playing a pivotal role in cancer management as proven by their efficacy evaluation studies. This review aims to fill the knowledge gaps by providing the preclinical evidence of cellular and molecular mechanisms of Indian phytomedicines in targeting varied pathways of breast cancer progression. A comprehensive search was performed on different platforms, followed by screening of relevant studies for review. In this article, the in-depth of various botanical drugs covering their nomenclature, dosage, toxicity, and modus operandi in BC cells have been extensively discussed. Various signaling pathways like Notch signaling, MAPK signaling, apoptosis, Wnt signaling, etc. regulated by herbal medicine treatment in BC are also highlighted to understand the drug mechanism better. This will guide the researchers to plan future strategies and generate more robust integrated evidence of plant-based drugs or botanical formulations for their potential role in the management of BC.

A short review on deciphering Vyadhikshamatva: insights from HLA-B27-ankylosing spondylitis relation.

OBJECTIVES: Various aspects of the concept of Vyadhikshamatva have been thoroughly explored, highlighting its profound significance in resisting disease manifestation, particularly in the context of Ankylosing spondylitis. Investigated the relationship between HLA-B27 and Ankylosing spondylitis (AS) by examining current knowledge and hypotheses Furthermore, efforts were made to portray the influence of prakruti (constitution) and balam (strength) on disease manifestation and progression. METHODS: Ayurvedic literature along with contemporary research works was analyzed for correlating various aspects like vyadhikshamatva,oja (The final essence of all body elements), and balam along with their influence on the defensive mechanism of the body. A thorough literature search was conducted to explore the strong association between HLA-B27 and AS by examining various hypotheses like the Arthritogenic peptide hypothesis, the Misfolding hypothesis, the Surface Homodimer hypothesis, and the ß2 microglobulin hypothesis that attempts to explain the pathogenic role of HLA-B27 in AS. Alongside classical Ayurvedic texts, databases like PubMed and Scopus were searched using keywords such as Immunity, Ankylosing spondylitis, Vyadhikshamatva, HLA-B27, Balam, and Autoimmune disorder with the help of Boolean operators. RESULTS: The review highlighted the critical role of Vyadhikshamatva in disease prevention, particularly in influencing the manifestation of conditions like AS despite genetic predisposition (HLA-B27). Further, the understanding of the Ayurvedic concepts can clearly explain the conflict that has arisen in the determination of the positive HLAB27 gene in Ankylosing Spondylitis as a definite diagnosing criteria. CONCLUSIONS: This comprehensive understanding will uplift the need for personalized medicine in disease management. Further research must be needed to understand the interaction between genetic factors (HLAb27), individual constitution, and their vyadikshamatva.

Adhatoda vasica and Tinospora cordifolia extracts ameliorate clinical and molecular markers in mild COVID-19 patients: a randomized open-label three-armed study.

BACKGROUND: SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. METHODS: A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19-65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. RESULTS: We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85-14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14-14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62-13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. CONCLUSIONS: All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27.

Dysmenorrhea and heavy bleeding as complications in COVID-19-positive women: An observational study.

Immunological dysregulation and inflammation may play a role in the nature of menstruation. Coronavirus disease 2019 (COVID-19) can produce a systemic inflammatory reaction that involves extrapulmonary organs and can also affect the immune system. This study aimed to analyze changes in the menstrual cycle in coronavirus (COVID)-positive women of reproductive age. Methods: The data of 35 women of reproductive age were collected telephonically from said patients admitted to the COVID Health Centre (CHC) ward of All India Institute of Ayurveda, New Delhi, during June 20, 2020, to October 31, 2020. Purposive sampling was used for data collection. Wyatt menstrual pictogram and Visual Analogue Scale (VAS) were used to assess the bleeding pattern and pain during menstruation, respectively. Results: Clinically, changes were noted in post-COVID menstruation such as irregularity, polymenorrhea, oligomenorrhea, clots, and menstrual flow in days. However, all results were statistically non-significant. But significant (P = 0.003) menstrual pain was reported. Conclusion: Menstrual changes were observed in COVID-19-positive women belonging to the reproductive age group.

Genome-wide DNA methylation profiling after Ayurveda intervention to bronchial asthmatics identifies differential methylation in several transcription factors with immune process related function.

BACKGROUND: The Indian traditional medicinal system, Ayurveda, describes several lifestyle practices, processes and medicines as an intervention to treat asthma. Rasayana therapy is one of them and although these treatment modules show improvement in bronchial asthma, their mechanism of action, particularly the effect on DNA methylation, is largely understudied. OBJECTIVES: Our study aimed at identifying the contribution of DNA methylation changes in modulating bronchial asthma phenotype upon Ayurveda intervention. MATERIALS AND METHODS: In this study, genome-wide methylation profiling in peripheral blood DNA of healthy controls and bronchial asthmatics before (BT) and after (AT) Ayurveda treatment was performed using array-based profiling of reference-independent methylation status (aPRIMES) coupled to microarray technique. RESULTS: We identified 4820 treatment-associated DNA methylation signatures (TADS) and 11,643 asthma-associated DNA methylation signatures (AADS), differentially methylated [FDR (≤0.1) adjusted p-values] in AT and HC groups respectively, compared to BT group. Neurotrophin TRK receptor signaling pathway was significantly enriched for differentially methylated genes in bronchial asthmatics, compared to AT and HC subjects. Additionally, we identified over 100 differentially methylated immune-related genes located in the promoter/5'-UTR regions of TADS and AADS. Various immediate-early response and immune regulatory genes with functions such as transcription factor activity (FOXD1, FOXD2, GATA6, HOXA3, HOXA5, MZF1, NFATC1, NKX2-2, NKX2-3, RUNX1, KLF11), G-protein coupled receptor activity (CXCR4, PTGER4), G-protein coupled receptor binding (UCN), DNA binding (JARID2, EBF2, SOX9), SNARE binding (CAPN10), transmembrane signaling receptor activity (GP1BB), integrin binding (ITGA6), calcium ion binding (PCDHGA12), actin binding (TRPM7, PANX1, TPM1), receptor tyrosine kinase binding (PIK3R2), receptor activity (GDNF), histone methyltransferase activity (MLL5), and catalytic activity (TSTA3) were found to show consistent methylation status between AT and HC group in microarray data. CONCLUSIONS: Our study reports the DNA methylation-regulated genes in bronchial asthmatics showing improvement in symptoms after Ayurveda intervention. DNA methylation regulation in the identified genes and pathways represents the Ayurveda intervention responsive genes and may be further explored as diagnostic, prognostic, and therapeutic biomarkers for bronchial asthma in peripheral blood.

AYURAKSHA, a prophylactic Ayurvedic immunity boosting kit reducing positivity percentage of IgG COVID-19 among frontline Indian Delhi police personnel: A non-randomized controlled intervention trial.

Objective: The world continues to face the COVID-19 crisis, and efforts are underway to integrate traditional medicine interventions for its effective management. The study aimed to determine the efficacy of the "AYURAKSHA" kit in terms of post-interventional percentage of COVID-19 IgG positivity, immunity levels, and quality of life (QoL) against COVID-19. Method: This was a non-randomized controlled, prospective intervention trial, done after the distribution of 80,000 AYURAKSHA kits (constituent of Sanshamani Vati, AYUSH Kadha, and Anu Taila) among Delhi police participants in India. Among 47,827 participants, the trial group (n = 101) was evaluated with the positivity percentage of IgG COVID-19 and Immune Status Questionnaire (ISQ) scores as a primary outcome and the WHO Quality of Life Brief Version (QOL BREF) scores along with hematological parameters as a secondary outcome in comparison to the control group (n = 71). Results: The data showed that the percentage of COVID-19 IgG positivity was significantly lower in the trial group (17.5 %) as compared to the control group (39.4 %, p = 0.003), indicating the lower risk (55.6%) of COVID-19 infection in the trial group. The decreased incidence (5.05%) and reduced mortality percentage (0.44%) of COVID-19 among Delhi police officers during peak times of the pandemic also corroborate our findings. The ISQ score and WHO-QOL BREF tool analysis showed the improved scores in the trial group when compared with the controls. Furthermore, no dysregulated blood profile and no increase in inflammation markers like C-reactive protein, erythrocyte sedimentation rate, Interleukin-6 (IL-6) were observed in the trial group. However, significantly enhanced (p = 0.027) IL-6 levels and random blood sugar levels were found in the control group (p = 0.032), compared to a trial group (p = 0.165) post-intervention. Importantly, the control group showed more significant (p = 0.0001) decline in lymphocyte subsets CD3+ (% change = 21.04), CD4+ (% change = 20.34) and CD8+ (% change = 21.54) levels than in trial group, confirming more severity of COVID-19 infection in the control group. Conclusion: The AYURAKSHA kit is associated with reduced COVID-19 positivity and with a better quality of life among the trial group. Hence, the study encourages in-depth research and future integration of traditional medicines for the prevention of the COVID-19 pandemic. Clinical trial registration: http://ctri.nic.in/, identifier: CTRI/2020/05/025171.

Ancient wisdom of ayurveda vis-à-vis contemporary aspect of materiovigilance.

Materiovigilance is regulatory system to study and follow incidents that might result from using medical devices. To trail the occurrence of untoward effects associated with medical devices as well as to document and prevent their recurrence; the Indian Pharmacopeia Commission initiated Materiovigilance program in India (MvPI) in 2015. Classical texts of Ayurveda include substantial description of devices intended for various therapeutic purposes such as Panchakarm (penta-bio purification procedures), Surgeries and for management of gynecological conditions etc. The implemented program of Materiovigilance does not include Ayurveda devices and thus there is need for documentation, systematic classification of Ayurveda devices and development of Ayurveda Materiovigilance (AMv). In this review, relevant information from classical texts of Ayurveda, latest published information related to Materiovigilance and information of medical devices from classical texts of Ayurveda has been scrutinized along with systematic correlation and applied interpretation of the collected data. It is observed that Materiovigilance has been well documented in Ayurveda in context of twenty six surgical and diagnostic devices; eleven mostly utilized pharmaceutical instruments five Panchakarma instruments and five home devices. For regulation of quality of Ayurveda medical devices, their manufacturing, standard utilization, reporting and prevention of medical device associated errors; it is the need of hour to create and implement regulation in the form of AMv. The Ayurveda literature highlights that the ancient seers of Ayurveda were well aware regarding Materiovigilance in their own way. However in view of modern era and mainstreaming of Ayurveda heritage, critical revision, updating, systematically categorization of Ayurveda devices, development and implementation of AMv regulation is the need of hour.

Efficacy of add-on Ayurveda and Yoga intervention in health care workers of tertiary care hospital during COVID-19: Randomized controlled trial.

BACKGROUND: The present study aimed to evaluate the safety and prophylactic efficacy of add-on Comprehensive Ayurveda and mindfulness-based Yoga (CAY) regimen to standard care among HealthCare Workers (HCWs) against COVID-19. MATERIALS AND METHODS: This prospective single-blind (outcome assessor-blinded) RCT was conducted in tertiary care hospital in Delhi during July 2020-April 2021. HCWs of both sexes were randomized to add-on CAY intervention or control group. The primary outcomes were the incidence of confirmed COVID-19 positive cases and influenza-like illness events (ILI). Secondary outcomes were anxiety (GAD-7), depression (PHQ-9), and quality of life (SF-36) at the end of 12 weeks. RESULTS: Three hundred fifty-six participants (181 in intervention and 175 in the control group) were randomized. With the modified intention to treat approach, we analyzed 309 participants. The mean age for the intervention and control group was 39.3 ± 10.1 and 36.6 ± 10 years, respectively. Incidence of COVID-19 event was higher in control group compared to CAY group (16 of 164 [9.8%] vs. 11 of 145 [7.6%]; P = 0.50). The incidence of ILI events was also higher in the control group as compared to the CAY group (14 of 164 [8.5%] vs 9 of 145 [6.2%]). The health change domain of the SF-36 questionnaire showed statistically significant improvement in the CAY group as compared to the control group (P < 0.01). CONCLUSION: Incidence of COVID-19 and ILI events was lower in the CAY group compared with the contr ol group, though the difference is not statistically significant.

Combating the psychological impact of COVID-19 pandemic through yoga: Recommendation from an overview.

Globally, the psychological health of the people is being affected due to the COVID-19 pandemic. Given the fact that numerous systematic reviews already exist on yoga and mental health, it becomes vital to undertake an overview on the same. The objective of the overview was to summarise the evidence from different systematic reviews of distinct yoga interventions used to improve mental health and recommend yoga practices for the same. The protocol was registered on PROSPERO (CRD42020185221). MEDLINE via Pubmed, Cochrane Database of Systematic Reviews and Google Scholar were searched for relevant literature. Search terms used were "Yoga practice, mental health and systematic review". Reviews from earliest possible date till May 2020, including those examining the effects of any single or combination of yoga interventions on mental health reported on children, youth and adults were selected. The Assessment of Multiple Systematic Reviews (AMSTAR) tool was used to evaluate the evidence of the included reviews. Out of the 90 reviews found, eight unique reviews were selected for the overview. Overall, 243 studies were analyzed, with an overlap of only 6 studies across the reviews. Out of 8 reviews, only 2 were of high quality and the rest were of moderate quality. Owing to heterogeneity of the included studies, only descriptive analysis was possible. The results of the review indicate moderate to positive effects of yoga on the mental health parameters. Practicing yoga (physical postures, Bhramary Pranayam, mindfulness meditation, sahaj yoga and laughter therapy) can be beneficial to improve psychological health of the people during the COVID-19 pandemic.

Immune status determined as per guidelines of Ayurveda found associated with clinical outcomes of COVID-19 disease - Results of a cross-sectional pilot study.

BACKGROUND: A key public health priority during the emergence of a novel pathogen is probing the factors contributing in clinical severity of the disease COVID-19. Moreover, analysis of the determined clinical outcomes is required and thus, modifiable predictor values need to identified. In Ayurveda, outcome of a disease is a multivariate function and this exploratory work is an attempt to identify one such factor "Vyadhiksamatwa" (immune status). MATERIALS AND METHODS: A questionnaire-based, cross-sectional study was conducted in fifty diagnosed cases of COVID-19. Study participants were subjected to a questionnaire to assess relationship between the three determinants of the disease - exposure, clinical severity, and Vyadhiksamatwa. RESULTS: Clinical severity was found strongly correlated with Vyadhiksmatwa with the value of Pearson Correlation - 0.740 significant at the 0.01 level (2-tailed). CONCLUSION: In the determination of clinical severity of disease, there are two epidemiological factors responsible - extrinsic (exposure) and intrinsic (Vyadhiksamatwa). It has been observed that higher the value of Vyadhiksamatwa of an individual, lesser will be the clinical severity of the disease in that individual. Vyadhiksamatwa can alter the host response to infections.

Neem (Azadirachta Indica A. Juss) Capsules for Prophylaxis of COVID-19 Infection: A Pilot, Double-Blind, Randomized Controlled Trial.

CONTEXT: SARS-CoV-2 is a global public-health concern. Interventions to prevent infection are urgently needed. The anti-inflammatory and antiviral effects of neem make it a potential agent for COVID-19 prophylaxis. OBJECTIVE: The study intended to evaluate the prophylactic effects of neem capsules for persons at high risk of COVID-19 infection due to contact with COVID-19 positive patients. DESIGN: The research team designed a prospective, randomized, double-blind, placebo-controlled, parallel-design study. SETTING: The study was conducted at a single center in India. PARTICIPANTS: Participants were 190 healthcare workers at the hospital or relatives of patients with COVID-19 infection. INTERVENTION: Of the 190 participants, 95 were in the intervention group and 95 in the control group. Participants received 50 mg of a proprietary, patent-pending, neem-leaf extract or a placebo orally in capsules, twice a day for 28 days. OUTCOME MEASURES: The number of individuals positive for COVID-19 between baseline and follow-up on day 56 was the primary outcome measure. Secondary measures included an evaluation of neem's safety and its effects on quality of life (QOL) and changes in biomarkers. RESULTS: The mean age of participants was 36.97 years, and 68.42% were male. Total 13 subjects tested positive during the study. All were asymptomatic. Of the 154 participants who completed the study per-protocol, 11 tested positive, 3 in the intervention group and 8 in the control group. The probability of COVID-19 infection in participants receiving the intervention was 0.45 times that of participants receiving the placebo, a relative risk of 0.45, with the effectiveness of the intervention being around 55%. Treatment-emergent adverse events (TEAEs) in both groups were minimal and were of grade 1 or 2 in severity. Biomarkers and QOL remained stable in both groups. CONCLUSIONS: The study found a reduced risk of COVID-19 infection in participants receiving neem capsules, which demonstrates its potential as a prophylactic treatment for the prevention of COVID-19 infection. The findings warrant further investigation in clinical trials.

All India AYUSH post graduate entrance exam 2019 - AYURVEDA MCQ item analysis.

BACKGROUND: AIAPGET 2019, an all India ranking entrance Test for MD/MS courses of Ayurveda, Unani, Siddha and Homeopathy stream was conducted by joint collaboration of National Testing Agency (NTA) and All India Institute of Ayurveda (AIIA). In this article, we present the item analysis of AIAPGET 2019 Ayurveda stream MCQs. OBJECTIVES: The aim of this article was to analyse the MCQs of AIAPGET 2019 of Ayurveda stream. MATERIALS AND METHODS: This exam was computer based conducted all over 25 centers across India. The question paper had 100 MCQs with 1 correct answer and 3 distractors for each item (Problem statement). RESULTS: AIAPGET 2019 question paper of Ayurveda stream had a Difficulty index of 37.32 ± 16.11 Discriminatory Index of 0.46 ± 0.27 and Distractor Index of 89 ± 17.8. CONCLUSION: Our analysis showed that though ideal, the question paper trended towards difficulty side.

Pharmacodynamic appraisal of wound-healing herbs of Sushruta Samhita.

Background: In Sushruta Samhita, various medicinal plants as single and compound formulations having Vrana-Shodhana (wound cleansing) and Vrana-Ropana (wound healing) potential are enumerated. There are no published data available on these wound-healing medicinal plants of Sushruta Samhita. The effectivee management of wound is necessary in the immunocompromised and chronic wounds patients as they take more time to heal. Aim: To review and systematically analyze wound-healing medicinal plants and their modus-operandi on the basis of pharmacodynamics attributes, i.e., Rasa (taste), Veerya (potency), and Vipaka (biotransformation) in the various stages of healing. Materials and methods: Review of Sushruta Samhita was done to gather wound-healing medicinal plants; pharmacodynamics attributes were gatherd from various Nighantus to understand their role in wound healing. The contemporary information about wound-healing mechanism was gathered from PubMed to interpitate the rational use of plants in the various stages of wound healing. Results: The study suggests that 43 medicinal plants have Vrana-Shodhana activity, 48 have Vrana-Ropana and 62 have both Vrana-Shodhana and Vrana-Ropana potential. Medicinal plants with Vrana-Shodhana category are having predominance of Katu (pungent), Tikta (bitter) and Kashaya (astriengent) Rasa. Plants under Vrana-Ropana are having Madhura, Kashaya Rasa (sweet taste), Madhura Vipaka (sweet biotransform) and Sheeta Veerya (cold potency). Conclusion: Plants having Tikta, Kashaya Rasa, Katu Vipaka, and Sheeta Veerya may be useful in the inflammatory stage, plants having Madhura, Kashaya Rasa and Sheeta Veerya may be useful in the prolifiratory stage and plants having Madhura Rasa, Sheeta Veerya, and Madhura Vipaka may be useful in the remodeling stage. The present review will help to give the directions to the researchers for the development of effective wound-healing medicines for wounds.

Dosha phenotype specific Ayurveda intervention ameliorates asthma symptoms through cytokine modulations: Results of whole system clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Over the past few decades, there have been significant scientific advances leading to improved understanding of asthma as a disease and treatment providing immediate relief. However, prevention of recurrent attacks, exacerbations and disease cure remains a challenge. Ayurveda refers to bronchial asthma as Tamaka Swasa and it is well explained in Charaka Samhita. Management of asthma in Ayurveda includes removal of vitiated Kapha through Shodhana, Shamana procedures, herbal and herbomineral formulations in addition to advising a healthy lifestyle and diet. Several clinical trials on Ayurvedic formulations for treatment of asthma are reported, however, whole system management of asthma has rarely been studied in the manner in which it is actually being practiced. Ayurveda therapeutics provides Dosha specific approaches, which needs biological investigation. AIM OF THE STUDY: The objective of our study was to investigate lung functions and cytokine changes in Asthmatic individuals in response to Ayurvedic intervention. METHODS: The study design was approved by the Institutional Ethics Committee of Tilak Ayurveda Mahavidyalaya (TAMV) & Sheth Tarachand Ramnath Charitable Ayurveda Hospital and followed guidelines of the Declaration of Helsinki and Tokyo for humans. It was conducted as a whole system individualized pragmatic clinical trial and written consent of patients was collected before enrollment. One hundred and fifteen patients with mild-to-moderate asthma were divided into 2 sub-groups depending on their disease subsets and administered phenotype specific ayurvedic interventions. Seventy six asthma patients completed the treatment. Serum IgE levels, blood eosinophil counts, spirometry and blood cytokine levels were measured before the start of treatment and six months at the end of treatment. Age and sex matched healthy participants (n=69) were recruited in the study for comparison of cytokines levels. RESULTS: Significant improvements in FEV1(% predicted) (p<0.0001) and FVC (% predicted) (p=0.0001) was observed in asthmatic patients who underwent Ayurvedic treatment. Circulating levels of IgE (p<0.03) and eosinophil numbers (p=0.001) reduced significantly in the asthmatics after Ayurvedic treatment. This was associated with significant reduction in levels of circulating cytokines. Levels of Th2, Th1 and inflammatory cytokines in the peripheral blood were higher than healthy control participants at baseline (p values <0.0001) and reduced significantly after ayurvedic intervention. CONCLUSION: This proof of concept study highlights the potential benefits and possible mechanism of Ayurvedic interventions in patients with mild-to-moderate asthma. The interventions significantly reduced IgE and eosinophil count, also improved lung function and reduced levels of circulating Th2 cytokines.