Synergistic Antibacterial Activity of Gallic Acid Based Chalcone Indl 2 by Inhibiting Efflux Pump Transporters.

As a part of novel discovery of drugs from natural resources, present study was undertaken to explore the antibacterial potential of chalcone Indl-2 in combination with different group of antibiotics. MIC of antibiotics was reduced up to eight folds against the different cultures of E. coli by both chalcones. Among the two compounds, the i. e. 1-(3', 4,'5'-trimethoxyphenyl)-3-(3-Indyl)-prop-2-enone (6, Indl-2), a chalcone derivative of gallic acid (Indl-2) was better along with tetracycline (TET) worked synergistically and was found to inhibit efflux transporters as obvious by ethidium bromide efflux confirmed by ATPase assays and docking studies. In combination, Indl-2 kills the MDREC-KG4 cells, post-antibiotic effect (PAE) of TET was prolonged and mutant prevention concentration (MPC) of TET was also decreased. In-vivo studies revealed that Indl-2 reduces the concentration of TNF-α. In acute oral toxicity study, Indl-2 was non-toxic and well tolerated up-to dose of 2000 mg/kg. Perhaps, the study is going to report gallic acid derived chalcone as synergistic agent acting via inhibiting the primary efflux pumps.

Program to Enhance Well-being and Psychospiritual Understanding Implications in Indian Medical Care Perspective.

BACKGROUND: Spirituality is an important dimension of life. The medical practitioner's well-being is an under-appreciated priority in India. As research on spirituality is minimal, this study attempts to introduce an online 6-week Eastern spirituality-based educational program for physicians. The primary aim was to see the effects of the intervention on the well-being of the participants. The secondary aim was to form an opinion about an extension to medical practice. MATERIALS AND METHODS: A total of 60 medical practitioners were randomized into two groups- one attended the spirituality sessions while the other placebo "self-care" sessions. Quantitative outcome measures were Warwick-Edinburg Mental Well-being Scale (WEMWBS) and World Health Organization (WHO) Well-being Index (WHO-5) noted pre and postprogram. Qualitative data was collected to support the quantitative outcomes. Statistical tests used were unpaired and paired t-tests for quantitative data. A 5-point Likert scale and Cochran's Q test were used for the qualitative data. RESULTS: In the spirituality group, postsession WEMWBS and WHO-5 scores improved with p < 0.0001 and p = 0.0033, respectively. Regarding qualitative data, 94.44% of physicians "agreed/strongly agreed" in favor of the benefits of sessions with p = 0.0242 and Q = 5.0793. A total of 86.67% of physicians felt the sessions have helped them to understand other's spirituality-related problems and made them more confident to discuss spirituality with others. CONCLUSION: The online Eastern spirituality program had a positive impact on the well-being of Indian medical practitioners. There appears to be a potential for extension to the medical care setting. The results need to be substantiated by further studies.

Rutin ameliorates malaria pathogenesis by modulating inflammatory mechanism: an in vitro and in vivo study.

Rutin (3, 3', 4' 5 and 7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid glycoside, found in many edible plants such as buckwheat and berries. Severe malaria is an inflammatory response triggered by oxidative stress that results in multi-organ pathologies and a high mortality rate in children and pregnant women worldwide. Rutin is recommended as a food supplement for the treatment of various diseases due to its anti-oxidative and anti-inflammatory properties, which prompted us to investigate its ameliorative effects in severe malaria pathogenesis against oxidative stress and inflammatory response using in vitro and in vivo bioassays. Rutin was examined in this work for its anti-plasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains, as well as its anti-oxidative and anti-inflammatory activity against LPS-stimulated macrophage cells. The in vitro data were subsequently verified in mice fed orally with rutin alone or in combination with chloroquine in Plasmodium berghei-induced malaria pathogenesis. The anti-plasmodial and anti-inflammatory properties of rutin were demonstrated in in vitro results. Apart from its anti-inflammatory and anti-oxidant effects in malaria pathogenesis, in vivo efficacy studies indicated that oral treatment with rutin reduced parasitaemia, increased mean survival time, and restored haemoglobin and glucose levels in mice at lower dose. Interestingly, both rutin and chloroquine demonstrated synergy in in vitro and in vivo experiments. The findings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria in combination with standard anti-malarial drugs.

Synthesis of thymol-based pyrazolines: An effort to perceive novel potent-antimalarials.

A series of thymol based substituted pyrazolines and chalcones was synthesized and evaluated for antimalarial activity, using in-vitro and in-vivo malaria models. All the target compounds (5a-k and 6a-j) were found to be active against human malaria parasite strain Plasmodium falciparum NF54. Among all, compounds 5e and 5f of chalcone series and 6c and 6f of pyrazoline series exhibited prominent antimalarial activity with IC50 less than 3 and 2 µM respectively, while other pyrazolines also significantly inhibited the P. falciparum with IC50 less than 10 µM. The designed pharmacophores were found to be effective against P. falciparum. Compound 6f was found to be able to retard malaria progression in mice. This was evident through decreased parasitemia, increased mean survival time and hemoglobin content in the treated animals. Moreover, 6f was observed as an inhibitor of heme polymerization pathway of the malaria parasite. It also inhibited free heme degradation, which could be possibly responsible for higher reactive oxygen species (ROS) in parasite, thus inhibiting the rapid proliferation of the parasite. In addition to this, compound 6f was found to be non-toxic with a good selectivity index. Based on these observations, the compound 6f could be taken up for further antimalarial lead optimization studies.

First Report of Plant-Derived ß-Sitosterol with Antithrombotic, in Vivo Anticoagulant, and Thrombus-Preventing Activities in a Mouse Model.

Inhibitors of thrombin, a key enzyme in the blood coagulation cascade, are of great interest because of their selective specificity and effectiveness in anticoagulation therapy against cardiovascular disorders. The natural soybean phytosterol, ß-sitosterol (BSS) demonstrated anticoagulant activity by dose-dependent inhibition of thrombin in an uncompetitive manner with a Ki value of 0.267 µM as well as by partial inhibition of thrombin-catalyzed platelet aggregation with a half-maximal inhibitory concentration (IC50) value of 10.45 ± 2.88 µM against platelet-rich plasma and 9.2 ± 1.2 µM against washed platelets. An in silico study indicated binding of BSS to thrombin, which was experimentally verified by spectrofluorometric and isothermal calorimetric analyses. Under in vitro conditions, BSS demonstrated thrombolytic activity by activating plasminogen, albeit it is devoid of protease (fibrinogenolytic) activity. BSS was noncytotoxic to mammalian cells, nonhemolytic, demonstrated its in vivo anticoagulant activity when administered orally, and inhibited k-carrageen-induced thrombus formation in the tails of mice. Our results suggest that dietary supplementation of BSS may help to prevent thrombosis-associated cardiovascular disorders.

Stiffness Percolation in Stochastically Fragmented Continua.

We study the mechanical behavior of three-dimensional, randomly microcracked continua for crack densities up to and above the transport percolation threshold. We show the existence of a fully fragmented material state in which stiffness is preserved due to topological interlocking of fragments. In this regime, the mechanical behavior is controlled by the contacts between fragments and becomes nonlinear. The upper limit of crack densities for which this behavior is observed, the stiffness percolation threshold, is identified. The variation of the effective material stiffness for crack densities ranging from 0 to the stiffness percolation threshold is reported.

Investigating Orientational Defects in Energetic Material RDX Using First-Principles Calculations.

Orientational defects are molecular-scale point defects consisting of misaligned sterically trapped molecules. Such defects have been predicted in α-RDX using empirical force fields. These calculations indicate that their concentration should be higher than that of vacancies. In this study we confirm the stability of a family of four orientational defects in α-RDX using first-principles calculations and evaluate their formation energies and annealing barrier heights. The charge density distribution in the defective molecules is evaluated and it is shown that all four orientational defects exhibit some level of charge reduction at the midpoint of the N-N bond, which has been previously related to the sensitivity to initiation of the material. We also evaluate the vibrational spectrum of the crystal containing orientational defects and observe band splitting relative to the perfect crystal case. This may assist the experimental identification of such defects by Raman spectroscopy.

Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

Drug Resistance Reversal Potential of Isoliquiritigenin and Liquiritigenin Isolated from Glycyrrhiza glabra Against Methicillin-Resistant Staphylococcus aureus (MRSA).

Isoliquiritigenin (ISL) and liquiritigenin (LTG) are structurally related flavonoids found in a variety of plants. Discovery of novel antimicrobial combinations for combating methicillin-resistant Staphylococcus aureus (MRSA) infections is of vital importance in the post-antibiotic era. The present study was taken to explore the in vitro and in vivo combination effect of LTG and ISL with ß-lactam antibiotics (penicillin, ampicillin and oxacillin) against mec A-containing strains of MRSA. Minimum inhibitory concentration (MIC) of both LTG and ISL exhibited significant anti-MRSA activity (50-100 µg/mL) against clinical isolates of MRSA. The result of in vitro combination study showed that ISL significantly reduced MIC of ß-lactam antibiotics up to 16-folds [∑ fractional inhibitory concentration (FIC) 0.312-0.5], while LTG reduced up to 8-folds (∑FIC 0.372-0.5). Time kill kinetics at graded MIC combinations (ISL/LTG + ß-lactam) indicated 3.27-9.79-fold and 2.59-3.48-fold reduction in the growth of clinical isolates of S. aureus respectively. In S. aureus-infected Swiss albino mice model, combination of ISL with oxacillin significantly (p < 0.05, p < 0.01, p < 0.001) lowered the systemic microbial burden in blood, liver, kidney, lung and spleen tissues in comparison with ISL, oxacillin alone as well as untreated control. Considering its synergistic antibacterial effect, we suggest both ISL and LTG as promising compounds for the development of novel antistaphylococcal combinations. Copyright © 2016 John Wiley & Sons, Ltd.

Potentiation of antimalarial activity of arteether in combination with Vetiver root extract.

In malaria, development of resistance towards artemisinin derivatives has urged the need for new drugs or new drug combinations to tackle the drug resistant malaria. We studied the fresh root extract of Vetiver zizanioides (Linn.) Nash (VET) with a CDRI-CIMAP antimalarial α/ß arteether (ART) together for their antimalarial potential. Our results showed additive to synergistic antimalarial activity of VET and ART with sum fractional inhibitory concentrations Σ FICs 1.02 ± 0.24 and 1.12 ± 0.32 for chloroquine sensitive (CQS) and chloroquine resistant (CQR) strain of Plasmodium falciparum (William H. Welch), respectively. Further, these combinations were explored against multidrug resistant rodent malaria parasite i.e. P. yoelii nigeriensis. Analysis of in vivo interaction of ART and VET showed that 10 mg/kg x 5 days of ART with 1000 mg/kg of VET x 5 days cured 100% mice infected with MDR parasite, while the same dose of ART could produce only up to 30% cure and VET fraction was not curative at all. Synergism/additiveness, found between VET and ART is reported for the first time. The curative dose of ART in the combination was reduced to its one fourth, and thus limits the side effects, if any. Although antimalarial potential of ART was enhanced by VET, action mechanism of later needs to be elucidated in detail.

Synthesis of neolignans as microtubule stabilisers.

Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20 µM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.

Naringin and chloroquine combination mitigates chloroquine-resistant parasite-induced malaria pathogenesis by attenuating the inflammatory response.

BACKGROUND: Malaria, characterised by inflammation and multi-organ complications, needs novel chemotherapeutics due to the rise of drug-resistant malaria parasites, which is a serious health issue. Naringin (NGN), a flavanone glycoside (naringenin 7-O-neohesperidose), has a broad spectrum of pharmacological activities but its effect against malaria, alone and in combination, was not deeply investigated. PURPOSE: To assess the pharmacological efficacy of NGN alone and in combination with chloroquine (CQ) against a Plasmodium strain resistant to CQ and to elucidate its potential mode of action. METHODS: The anti-inflammatory potential of NGN was assessed in mouse microglial cells stimulated with hemozoin by analyzing inflammatory cytokines production. The anti-plasmodial potential of NGN was subsequently tested alone and in combination with CQ against the K1 strain of Plasmodium using the fixed ratio combination method. Further, we evaluated NGN's antimalarial efficacy against the CQ-resistant Plasmodium yoelii nigeriensis N67 strain (P. yoelii), both alone and in combination with CQ, by measuring parasitemia and survival rates. To comprehend the impact of NGN on malaria-induced inflammation in mice, we measured pro-inflammatory cytokines elevated by activated NF-кB signalling. These findings were supported by mRNA and immunohistochemical analyses of malaria-infected mice's liver and brain tissues. RESULTS: Our study demonstrated that NGN displayed anti-plasmodial activity, which was further augmented when combined with CQ. At 50 µM, NGN significantly reduced the elevation of pro-inflammatory cytokines in synthetic hemozoin-stimulated microglial cells. Compared to P. yoelii-infected mice, NGN (12.5 mg kg-1) significantly reduced parasitemia in mice, resulting in a survival period of up to 13 days. Survival improved by up to 20 days when NGN and CQ were given in combination. NGN, as revealed by immunohistochemical examination of brain and liver tissues, interfered with the NF-кB pathway, potentially reducing the elevation of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-18, IFN-γ, and IL-6). This was supported by the overexpression of inflammation-regulatory genes (TGFß, Nrf2, HO-1, and iNOS) and the downregulation of inflammation-stimulating genes (NF-κB, NLRP3, and caspase-1). Histopathological analysis demonstrated the potential of NGN to restore liver and brain tissues to normal. The substantial decrease in the expression and production of ICAM-1 protein in the brain tissue implies the beneficial effects of NGN, pointing towards its potential for mitigating brain pathology. CONCLUSION: The findings of this study revealed NGN as a promising drug-like candidate for the management of CQ-resistant parasite-induced malaria pathogenesis for adjunctive therapy in combination with standard antimalarial drugs through its modulation of the NF-κB-mediated inflammation.

Cu-catalyzed click reaction in synthesis of eugenol derivatives as potent antimalarial agents.

Eugenol(1), a terpenoid found in Ocimum, has various biological activities. The present study aims at extraction, isolation of the plant secondary metabolite eugenol (1), it's derivatisation and structure identification as bioactive molecules. Synthesis and antiplasmodial activity (in-vitro and in-vivo), of a series of fourteen novel eugenol-based 1,2,3-triazole derivatives was done in the present study. Derivatives 5a-5n showed good antimalarial activity against the strain Plasmodium falciparum NF54. Derivative 5 m, IC50 at 2.85 µM was found to be several times better than its precursor 1 (106.82 µM) whereas the derivative 5n showed three fold better activity than compound 1, in vitro. The structure-activity relationship of the synthesised compounds indicated that the presence of triazole ring in eugenol analogues is responsible for their good activity. Compound 5m, was further evaluated for in-vivo antimalarial activity which showed about 79% parasitemia suppression. It is the first report on antimalarial activity of triazole eugenol derivatives.

Gallic Acid Derived 1, 2-Diarylindole as a Potential Antifungal Agent against Candida Strain.

BACKGROUND: In recent decades, Candida albicans has become a serious issue for public health. The worldwide rapid rise in drug resistance to conventional therapies is the main contributing reason. Moreover, because of their potent activity at low concentrations and apparent lack of toxicity, compounds originating from plants are used in therapeutic treatments because of their potent activity at low concentrations and apparent lack of toxicity. Particularly in immunocompromised people, Candida species can result in a wide range of ailments. OBJECTIVES: Present manuscript describes antifungal activity of an indole derivative 1-(4-((5- methoxy-2-(3,4,5-trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1- amine (7, 100DL-6) by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS- Delhi). METHODS: The synthetic strategy for the preparation of indole derivatives was modified through Fischer indole reaction. Antifungal activity of an indole derivative 1-(4-((5-methoxy-2-(3,4,5- trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (7, 100DL-6) was done by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS-Delhi). Compound 100DL-6 efficacy was determined by Combination synergy study, ergosterol binding assay, MTT toxicity study and Mutagenicity. RESULTS: Compound 100DL-6 was obtained in 65% yield on desired motifs. Docking scores found were 100DL-6 (-8.7 kcal/mol) and Fluconazole (-7.6 kcal/mol). Further, RMSD were shown for 100DL6 (0.26 ± 0.23 nm) and fluconazole (1.2 ± 0.62 nm). Indole derivative 100DL-6 was active against the tested fungal pathogens and the total zone of inhibition was measured between 13-14 mm in diameter and MIC values between 31.25 µg/mL to 250 µg/mL and MFC values between 62.5 µg/mL to 500 µg/mL. In checkerboard assay synergistic mode of interaction of 100DL-6 with known antifungal drugs was observed. In the presence of ergosterol 100DL-6 and standard drug (s) increased their MIC values, demonstrating a considerable affinity for ergosterol. Compound 100DL-6 was considered to be less-cytotoxic to the cells as determined by MTT assay. Lead compound 100DL-6 was found to be non-mutagenic. CONCLUSION: In the present study, 100DL6 (indole derivatives) significantly abrupted the ergosterol biosynthetic pathway and showed moderate anti-candidal effects. These studies suggest that 100DL6 significantly enhances antifungal effect of clinical drug fluconazole synergistically and may be considered as in clinical trial prior to some extensive in-vivo validations.

Understanding the function of Pax5 in development of docetaxel-resistant neuroendocrine-like prostate cancers.

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small-cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression databases indicates that t-NEPC upregulates various neuronal pathways associated with enhanced cellular networks. To identify transcription factor(s) (TF) that could be important for promoting the gene expression for neuronal characters in t-NEPC, we performed ATAC-Seq, acetylated-histone ChIP-seq, and RNA-seq in our NE-like cell line models and analyzed the promoters of transcriptionally active and significantly enriched neuroendocrine-like (NE-like) cancer-specific genes. Our results indicate that Pax5 could be an important transcription factor for neuronal gene expression and specific to t-NEPC. Pathway analysis revealed that Pax5 expression is involved in axonal guidance, neurotransmitter regulation, and neuronal adhesion, which are critical for strong cellular communications. Further results suggest that depletion of Pax5 disrupts neurite-mediated cellular communication in NE-like cells and reduces surface growth factor receptor activation, thereby, sensitizing them to docetaxel therapies. Moreover, t-NEPC-specific hydroxymethylation of Pax5 promoter CpG islands favors Pbx1 binding to induce Pax5 expression. Based on our study, we concluded that continuous exposure to ARSI therapies leads to epigenetic modifications and Pax5 activation in t-NEPC, which promotes the expression of genes necessary to adopt taxane-resistant NE-like cancer. Thus, targeting the Pax5 axis can be beneficial for reverting their taxane sensitivity.

In vivo efficacy and synergistic interaction of 16α-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide, a clerodane diterpene from Polyalthia longifolia against methicillin-resistant Staphylococcus aureus.

The Staphylococcus aureus bacterium, a nosocomial pathogen often causing untreatable and lethal infection in patients, mutated to become resistant to all the first-line drugs. The present study details the potential of clerodane diterpene 16α-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide (CD) isolated from Polyalthia longifolia against methicillin-resistant S. aureus (MRSA) through in vitro and in vivo assays. Minimum inhibitory concentration (MIC) of CD exhibited significant anti-MRSA activity (15.625-31.25 mg/l) against reference strain and seven clinical isolates, while time kill assays at graded MICs indicated 2.78-9.59- and 2.9-6.18-fold reduction in growth of reference strain and clinical isolates of S. aureus, respectively. The combined effect of the CD and 7.5 % NaCl resulted in significant reduction in microbial count within 24 h, indicating the loss of the salt tolerance ability of S. aureus. Further, release of 260-nm absorbing material and flow cytometric analysis revealed an increased uptake of propidium iodide. These assays may indicate the membrane-damaging potential of CD. The molecule CD was found to interact synergistically with clinically used antibiotics (FICI ≤ 0.5) against all clinical isolates. In infected mice, CD significantly (P < 0.001) lowered the systemic microbial load in blood, liver, kidney, lung and spleen tissues and did not exhibit any significant toxicity at 100 mg/kg body weight.

Nyctanthes arbor-tristis positively affects immunopathology of malaria-infected mice prolonging its survival.

In order to search for new products that display antimalarial and immunomodulatory mechanisms that complement direct antiparasitic activity, a set of in vitro and in vivo experiments were designed to evaluate the effect of Nyctanthes arbor-tristis in Plasmodium berghei infected mice. Three extracts of N. arbor-tristis leaves from varying concentrations of alcohol and water were considered for their potential to suppress expression of pro-inflammatory mediators from macrophages primed with lipopolysaccharide. The ethanolic extract, which lowered the pro-inflammatory mediators [tumour necrosis factor (TNF), 13.52-55.83 %; interleukin-6 (IL-6), 0-17.29 %; and NO, 39.37-81.63 %], was selected to be examined in malaria (P. berghei) infected mice. Corroborating the in vitro results, it was observed that the extract could normalise the TNF (78 %) and IL-6 (70.35 %) optimally at 1 g/kg, thus retarding the pathological process in infected mice and increasing the mean survival time from 10.6 to 15.6 days. There were no signs of toxicity in the acute oral toxicity test up to 2 g/kg. (1)H NMR of the biologically active extract was obtained to ensure the presence of the compound of interest, i.e., iridoid glycoside. The quality and the reproducibility of results were ensured by means of achieving characteristic high-performance liquid chromatography fingerprint of the extract.

Mindfulness influences the psycho-social dimension of chronic pain: A randomized controlled clinical trial in Indian context.

Background and Aims: In India, the awareness about the psycho-social dimension of chronic pain is minimal among physicians and patients. The research with community-based group therapies (like mindfulness) to address the psycho-social aspects in chronic pain patients remains limited. The aim of this randomized controlled trial was to see the effects of mindfulness on pain intensity, pain catastrophizing, chronic pain acceptance, perceived stress, well-being, and mindfulness characteristics. Materials and Methods: In this two-site, parallel group, clinical trial, 170 patients attending pain outdoors of two government hospitals in West Bengal, India, were randomized to attend five weekly in-person mindfulness sessions (cases) or usual care sessions (controls) within the hospital premises. Pre-program and post-program data were collected and analyzed using statistical methods like repeated measures analysis of variance. Results: In participants of the mindfulness group, significant changes post session were noted in pain intensity [F(1,326) = 15.0122; P = 0.0001291], pain acceptance [F(1,326) = 4.5311; P = 0.03403], and perceived stress score [F(1,326) = 13.2788; P = 0.0003122] compared to pre-session. The changes in pain catastrophizing, World Health Organization well-being and Freiburg mindfulness inventory scores were non-specific. Conclusion: Mindfulness had a positive influence on pain intensity, pain acceptance, and perceived stress of Indian chronic pain patients. The effects on pain catastrophizing, mindfulness characteristics, and well-being (non-specific) were also encouraging. Further studies will be required to substantiate these results.

Quebrachitol from Putranjiva roxburghii Wall. (Putranjivaceae) a potent antimalarial: Pre-clinical efficacy and its interaction with PfLDH.

Researchers are exploring natural resources in search of a new and effective anti-malarial compound to address the challenges in malarial treatment due to emerging incidences of drug-resistant strains. Following background knowledge of traditional medicine, we evaluated the in-vitro and in-vivo anti-malarial efficacy of Putranjiva P. roxburghii (Putranjivaceae) twigs ethanol extracts and fraction (PRT). In-vitro parasite-specific lactate dehydrogenase (pLDH) assay was performed using a chloroquine-sensitive Plasmodium falciparum strain. The results of the in-vitro study were further validated by in-vivo anti-malarial studies on P. berghei Keyberg 173 (K173) infected mice. The crude ethanol extract of the PRT showed the most moderate antiparasitic activity (IC50 = 15.51 µg/mL). In contrast, its butanol fraction extract showed potent activity (IC50 = 5.14 µg/mL) with a selectivity index (SI) of 28.87. Two phytochemicals, viz. 2, 4 dihydroxy-5-(hydroxymethyl) benzoic acid (DHMBA), and quebrachitol (QBC), were identified with anti-parasitic activity (IC50 = 5.01 µg/mL and 0.87 µg/mL) and selectivity index (SI) of 45 and 158. The in-vivo studies confirmed the significant anti-malarial activity of QBC at the dose of 30 and 60 mg/kg body weight with chemo-suppression values of 73.26% and 61.88%, respectively. The present study demonstrates the bioactive marker-based standardization of P. roxburghii twig, the antiplasmodial potential of PRT, and the role of QBC in suppressing parasitemia. The findings of the study support QBC as a prospective lead for a natural product-based adjunct remedy to conventional antiparasitic agents for malarial infectious.

A randomized controlled pilot study of add-on therapy of CIM-MEG19 (standardized Andrographis paniculata formulation) in mild to moderate COVID-19.

Background: Traditional knowledge and scientific shreds of evidence strongly support the repurpose of Kalmegh (Andrographis paniculata, CIM-MEG19) as an alternate therapy for prophylactic management and treatment of severe acute respiratory syndrome coronavirus (SARS-CoV) and associated health disorders. Purpose: The study aimed to assess the efficacy and safety of the CIM-MEG19 (standardized A. paniculata extract formulation), a proprietary Ayurvedic medicine in the COVID-19 management, clinical recovery, and outcomes in terms of hospitalization days as well as any sign of severity due to drug-drug interaction between CIM-MEG19 TM and standard of care (SoC). Methods: A randomized, parallel-group, active-controlled interventional pilot clinical study was conducted. The Group-A subjects were assigned to CIM-MEG19 add-on to SoC treatment using modern medicine without antiviral drug whereas Group-B patients with SoC treatment using modern medicine and recommended antiviral drug for COVID-19 management. Eighty RTPCR (real-time polymerase chain reaction) positive and eligible COVID-19 patients of age >18 years, having mild or moderate severity, were enrolled. Results: Clinical improvement in reduction of symptoms showed significant (p<0.0001) results in the average days in subjects of group-A (Investigational intervention arm) compared to Group B (SoC). The RT-PCR investigation exhibited COVID negative for 50 % in CIM-MEG19 add-on and 47% in SoC treatment after 8-11 days. Similarly, biochemical investigations showed that CIM-MEG19 group-A had a significant (p ≤ 0.05) effect on C-Reactive Protein (CRP) and Interleukin-6 (IL-6) after 14 days of treatment. Additionally, improvement in D-Dimer, ESR, and LDH in CIM-MEG19 add-on therapy was also observed. Conclusions: The study demonstrated an excellent safety profile, declining the severity of the infection and halting the disease advancement/progression. CIM-Meg19 might be used as a potential natural drug for treating COVID-19.