A multivariate and quantitative assessment of medicinal plants used by the indigenous Malayali tribes in the Javadhu hills of Tiruvannamalai district, Tamil Nadu, India.

The study of medicinal plants with their traditional uses and related pharmacological studies has received more attention during the past several decades around the world. The Malayali tribes of the Javadhu Hills in the Eastern Ghats rely heavily on a system of traditional medicine for healthcare. A qualitative ethnographic method with a semi-structured questionnaire was used to interview 52 people across 11 localities in the Javadhu Hills. In the data analysis, descriptive statistics such as Use reports (UR), frequency of citations (FC), relative frequency of citations (RFC), informant agreement ratio (IAR), fidelity level (FL), and informant consensus factor (FIC) were studied. In the current investigation, 146 species from 52 families and 108 genera were discovered to treat 79 diseases. Leguminosae and Apocynaceae were the dominant families (12 species each). The most frequently used life form was the herb and the plant part were the leaf. The majority were being harvested from natural resources. Most medicines were taken orally. The most frequently cited species are Moringa oleifera and Syzygium cumini. The illnesses were divided into 21 categories. The majority of the plants mentioned are utilised to increase human immunity and health. The principal ailment (general health) was revealed by two-way cluster analysis and PCA. The species Litsea decanensis, Phoebe paniculata, Commiphora caudata, etc., were new records for the Javadhu hills according to a comparison between the current study and previous local and regional research. Documenting novel ethnomedicinal species and their therapeutic applications will encourage more phytochemical and pharmacological research and may even result in the creation of new medications. Furthermore, the study's significant novelty is that principle component analysis and two-way cluster analysis clearly revealed that the species that are used to treat various diseases, as well as species that are closely associated with treating specific ailment categories, are distinct. Significantly, species recorded in this study rely on maintaining and improving general body health of humans.

A semi purified hydroalcoholic fraction from Caesalpinia bonduc seeds causes ergosterol biosynthesis inhibition in Candida albicans resulting in cell membrane damage.

Candida species are currently developing resistance to prevailing commercially available drugs, which raises an instantaneous need to discover novel antifungals. To cope with this shocking situation, phytochemicals are the richest, safest, and most potent source of excellent antimicrobials with broad-spectrum activity. The aim of the current study is to explore the anticandidal potential of the various fractions purified from the hydroalcoholic extract of C. bonduc seed. Out of five fractions purified from the hydroalcoholic extract, fraction 3 (Fr. 3) recorded the best activity against C. albicans (8 µg/mL) and thus this species was chosen for further mechanism of action studies. The phytochemical examination reveals that Fr. 3 was found to contain steroids and triterpenoids. This was further supported by LC-QTOF-MS and GCMS analyses. Our findings show that Fr. 3 targets the ergosterol biosynthesis pathway in C. albicans by inhibiting the lanosterol 14-α demethylase enzyme and downregulating expression of its related gene ERG11. Molecular docking outcomes disclosed favorable structural dynamics of the compounds, implying that the compounds present in Fr. 3 would be able to successfully bind to the lanosterol 14-α demethylase, as evidenced by the docked compounds' strong interaction with the target enzyme's amino acid residues. Considering virulence factors, the Fr. 3 recorded significant antibiofilm activity as well as germ-tube reduction potential. Furthermore, Fr. 3 enhances the production of intracellular reactive oxygen species (ROS). This suggests that the antifungal activity of Fr. 3 was associated with membrane damage and the induction of ROS production, resulting in cell death. Fluorescence microscopic analysis of PI stained Candida further showed changes in the plasma membrane permeability, which causes severe loss of intracellular material and osmotic balance. This was demonstrated by the potassium ion leakage and release of genetic materials. Finally, the erythrocyte lysis assay confirmed the low cytotoxicity of Fr. 3. Both in silico and in vitro results suggest that Fr. 3 has the potential to propel forward novel antifungal drug discovery programmes.

Pharmacological Evaluation of the Anesthetic and Analgesic Potential of Injection Harsha 22: A Novel Polyherbal Local Anesthetic Formulation Intended for Parenteral Administration in Wistar Albino Rats.

Background: Local anaesthetics are medications that cause numbness that can be reversed by applying them topically. Local anaesthetics are clinically used to control pain during minor surgeries or to treat other acute and chronic pain. The present investigation intended to investigate the anesthetic as well as analgesic potential of Injection Harsha 22, a novel polyherbal formulation in Wistar albino rats. Methods: The anesthetic potential of Injection Harsha 22 was evaluated by a heat tail-flick latency (TFL) test, whereas the analgesic effect was elevated by electrical stimulation testing. Here, lignocaine (2%) was used as the standard anesthetic drug. Results: In TFL, Injection Harsha 22 showed anesthetic effects up to 90 minutes after application. Also, the duration of anesthesia in rats that were administered subcutaneously with Injection Harsha 22 was comparable to that of the rats treated with commercial lignocaine (2%). In an electrical stimulation test, single administration of Injection Harsha 22 to rats significantly prolonged analgesia compared with the normal control group. The median duration of analgesia in rats administered subcutaneously with Injection Harsha 22 and lignocaine solution was 40 minutes and 35 minutes, respectively. Furthermore, Injection Harsha 22 does not interfere with the hematopoietic system of the experiment animals. Conclusion: Thus, the present investigation established the in vivo anesthetic and analgesic potential of Injection Harsha 22 in experimental animals. Hence, it can be concluded that Injection Harsha 22 can become a prominent substitute for lignocaine as a local anaesthetic agent after establishing its efficacy through stringent clinical trials in humans.

An efficacy and safety report based on randomized controlled single-blinded multi-centre clinical trial of ZingiVir-H, a novel herbo-mineral formulation designed as an add-on therapy in adult patients with mild to moderate COVID-19.

OBJECTIVE: Coronaviruses, hence named because of the crown-like spikes on the viral envelope, are members of Coronaviridae family and Order Nidovirales. SARS-CoV-2 is the seventh human pathogenic coronavirus identified after HCoV-229E, HCoV-OC43, SARS-CoV (SARS-CoV-1), HCoV-NL63, CoV-HKU1, and MERS-CoV. SARS-Cov-2 is highly similar to SARS-CoV. COVID-19 is the corresponding acute disease caused by SARS-CoV-2 that was initially reported in Wuhan, China towards the end of 2019 and spread to millions of humans globally. Unfortunately, limited studies were available on the efficacy of antiviral drugs to treat COVID-19 at the time of this study. ZingiVir-H is an Ayurvedic formulation for use in early therapy of viral disease. This clinical trial was planned to investigate (1) the efficacy and safety of ZingiVir-H and (2) the efficacy of ZingiVir-H as an add-on therapy to the standard of care in hospitalized adults diagnosed with COVID-19. METHODS: A total of 123 eligible subjects as per inclusion criteria were randomized within the study. Three subjects later declined to participate in the study and four subjects didn't meet inclusion criteria, which brought the final evaluable subject count to 116 for the efficacy and safety endpoint analysis. Thus, a total of 116 patients were equally randomised into two groups, namely, ZingiVir-H and Placebo for this clinical trial. The study patients were assigned to receive either ZingiVir-H or Placebo along with the standard of care as per the National Indian COVID-19 treatment protocol. The time interval until a negative RT-PCR obtained, was evaluated during treatment with ZingiVir-H or Placebo for ten days. Liver and kidney function tests were regularly assessed to ensure the safety profile of ZingiVir-H. RESULTS: The study found that patients who were administered ZingiVir-H had a median recovery time of 5 days (95% confidence interval (CI) 5-5) when compared to 6 days (95% CI 5-6) in those who received Placebo. Besides, in Ordinal Scale analysis of all the patients treated with ZingiVir-H demonstrated significant redistribution to a better clinical status from ordinal scale 5 to 6 and 7 within five to seven days when compared to that of placebo treatment. The time required for clinical improvement and the number of days needed for hospitalization was significantly less in the ZingiVir-H treated group when compared to placebo. The absence of liver and kidney function changes affirmed the safety profile of ZingiVir-H. No serious adverse events were reported in ZingiVir-H treated patients. CONCLUSION: We found that ZingiVir-H is effective and safe in managing COVID-19 infections and delaying the disease progression from mild to moderate and moderate to severe. To the best of our knowledge, this is the first clinical trial report on the efficacy/safety of a herbo-mineral Ayurvedic drug against COVID-19 as of yet. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2020/04/024883. Registered on 28/04/2020.

Ethanolic extract of Caesalpinia bonduc seeds triggers yeast metacaspase-dependent apoptotic pathway mediated by mitochondrial dysfunction through enhanced production of calcium and reactive oxygen species (ROS) in Candida albicans.

Candida albicans is a widespread disease-causing yeast affecting humankind, which leads to urinary tract, cutaneous and various lethal systemic infections. As this infection rate steadily increases, it is becoming a significant public health problem. Recently, Caesalpinia bonduc has received much attention from researchers due to its diverse pharmacological properties, including antimicrobial effects. Accordingly, we first planned to explore the in-vitro anticandidal potential of three extracts obtained from C. bonduc seeds against four Candida species. Initially, the anticandidal activity of the seed extracts was checked by the microdilution technique. Out of three seed extracts tested, ethanolic extract of C. bonduc seed (EECS) recorded the best activity against C. albicans. Hence, we next aimed to find out the anticandidal mechanism of EECS in C. albicans. The liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analysis showed that the major compounds present in the EECS were tocopherols, fucosterol, linoleic acid, ß-amyrin, ß-sitosterol, campesterol, cassane furanoditerpene, Norcassane furanoditerpene and other diterpenes. To evaluate the cell death mechanism in C. albicans, a series of parameters related to apoptosis, viz., reactive oxygen species (ROS) production, membrane permeability, mitochondrial membrane potential, release of cytochrome c, DNA fragmentation, nuclear condensation, increased Ca2+ level in cytosolic and mitochondrial and activation of metacaspase, were analyzed. The results showed that EECS treatment resulted in the elevation of ROS, which leads to plasma membrane permeability in C. albicans. Annexin V staining further confirms the early stage of apoptosis through phosphatidylserine (PS) externalization. We further inspected the late apoptotic stage using DAPI and TUNEL staining assays. From the results, it can be concluded that EECS triggered mitochondrial dysfunction by releasing high levels of ROS, cytochrome c and Ca2+resulting in the activation of metacaspase mediated apoptosis, which is the central mechanism behind the cell death of C. albicans. Finally, a Galleria mellonella-C. albicans infection system was employed to assess the in-vivo potential of EECS. The outcomes displayed that the EECS considerably enhanced the recovery rate of G. mellonella larvae from infection after the treatment. Additionally, EECS also recorded low hemolytic activity. This study thus spotlights the anticandidal potential and mechanism of action of EECS against C. albicans and thus delivers a promising treatment approach to manage C. albicans infection in the future.

Administration of Caesalpinia bonduc Seed Extracts Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia (BPH) in Male Wistar Rats.

Introduction: Benign prostatic hyperplasia (BPH) is a major chronic disease affecting men, and the therapeutic agents currently used to manage it have significant side effects. As a result, an alternative medicine with improved therapeutic properties with no side effects is desperately needed. The current investigation aims to study whether the Caesalpinia bonduc seed extracts (ethanolic-A, hydroalcoholic-B, and aqueous-C) have inhibitory potential on testosterone propionate (TP)-induced BPH in Wistar rats. Methods: Wistar rats (male) were randomly allocated to one of five groups: control, BPH (TP-3 mg/kg, subcutaneously daily), low dose (TP + C. bonduc seed extracts - 200 mg/kg body weight), high dose (TP + C. bonduc seed extracts - 400 mg/kg body weight), and standard drug (TP + finasteride - 10 mg/kg body weight). At the end of drug treatment, the rats were sacrificed and their serum and prostates were taken for biochemical and histological studies. Results: C. bonduc seed extracts treatment significantly decreased prostate weight and prostatic index in rats with TP-induced BPH. The seed extracts exhibited a potent inhibitory effect on dihydrotestosterone (DHT) in serum and prostate. In addition, the PSA level in the serum showed a noteworthy decrease in comparison with the BPH group. Histopathological examination also indicated that extracts improved the tissue morphology of the prostate significantly. Out of three extracts tested, ethanolic and hydroalcoholic extract recorded significant effect. Finally, liquid chromatography quadrupole time-of-flight mass spectrometry (LC/MS-QTOF) analysis showed that the major compounds present in the extracts were tocopherols, fucosterol, linoleic acid, ß-amyrin, ß-sitosterol, campesterol, cassane furanoditerpene, norcassane furanoditerpene and other diterpenes. Conclusion: Thus, C. bonduc seed extracts could be a potential source for the formulation of new drug for managing BPH. To the best of our knowledge, this is the first scientific animal investigation into the use of C. bonduc seed extract for the management of BPH.