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Saswati Banerjee,1,* Niladri Mukherjee,1,* Rahul L Gajbhiye,2 Snehasis Mishra,1 Parasuraman Jaisankar,2 Sriparna Datta,3 Krishna Das Saha1 1Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India; 2Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India; 3Department of Chemical Technology, University of Calcutta, Kolkata 700009, India*These authors contributed equally to this workCorrespondence: Krishna Das SahaCancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, IndiaTel +91 0 332 499 5810Email krishna@iicb.res.inBackground: Many of present chemotherapeutics are inadequate and also resistant against visceral leishmaniasis (VL), an immunosuppressive ailment caused by Leishmania donovani. Despite the interest in plant-based drug development, no antileishmanial drugs from plant source are currently available. Glinus oppositifolius had been reported in favor of being immune modulators along with other traditional uses. Novel anti-VL therapies can rely on host immune-modulation with associated leishmanicidal action.Objective: Discovery of novel plant-based antileishmanial compound from G. oppositifolius having permissible side effects.Methods: With this rationale, an n-BuOH fraction of the methanolic extract of the plant and obtained triterpenoid saponin Spergulin-A were evaluated against acellular and intracellular L. donovani. Immunostimulatory activity of them was confirmed by elevated TNF-α and extracellular NO production from treated MФs and was found nontoxic to the host cells. Identification and structure confirmation for isolated Spergulin-A was performed by ESI-MS,13C, and 1H NMR.Results: Spergulin-A was found ineffective against the acellular forms while, against the intracellular parasites at 30 μg/mL, the reduction was 92.6% after 72 hrs. Spergulin-A enhanced ROS and nitric oxide (NO) release and changes in Gp91-phox, i-NOS, and pro and anti-inflammatory cytokines elaborated its intracellular anti-leishmanial activity.Conclusion: The results supported that G. oppositifolius and Spergulin-A can potentiate new lead molecules for the development of alternative drugs against VL.Keywords: visceral leishmaniasis, Glinus oppositifolius, spergulin-A, macrophage, immunostimulation, anti-amastigote

The leaves of Pterocarpus santalinus have been identified as a good source of health-beneficial flavonoids through the amalgamation of untargeted metabolomics using UHPLC-ESI-MS n leading to the identification of flavone-glycosides bearing isorhamnetin and quercetin skeletons. To unveil the optimum ultrasonication extraction conditions required for the comprehensive extraction of major flavone-glycosides, isorhamnetin-3-O-β-d-(2-O-α-L-rhamnopyranosyl)glucopyranoside and isorhamnetin-3-O-β-d-glucopyranoside, the response surface methodology based on Box-Behnken design was adopted. The influence of input extraction parameters extraction time (X 1 ): 15-45 min, temperature (X 2 ): 40-60 °C and biomass-solvent ratio (X 3 ): 60-100 on the extractive yield and comprehensive flavonoid content resulted in the optimal conditions as 19.09 min, 48.65 o C, and 72.15, respectively. The investigation provides a sustainable approach for recovering health-beneficial flavone-glycosides for utilization in various industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Bergenia ciliata (Haw.) Sternb. (Family Saxifragaceae) remains mentioned as Pashanbheda in Ayurveda and Zakhmehayat in Unani. In North Waziristan, Pakistan, indigenous communities use this plant in ethnodentistry to treat tooth decay and toothaches. However, scientific evidence on its mode of action is still lacking., Aim of the Study: To evaluate the effect of extracts and fractions of B. ciliata flower against oral bacteria and elucidate the possible antibacterial and antibiofilm mechanism., Materials and Methods: Prepared extract of B. ciliata flowers were checked for its antibacterial activity against oral (S. mutans, S. pyogenes, S. oralis) and opportunistic bacteria (Staphylococcus aureus, Citrobacter clonae and Achromobacter insolitus). Preparative TLC-bioautography and silica gel column chromatography was used to isolate bioactive compounds. HRESI-MS and NMR studies were employed for its structural elucidation. Antibacterial and antibiofilm activities of extracts and isolated compounds were studied against S. mutans. Scanning Electron Microscope studies indicated membrane damage. Reactive Oxygen Species (ROS) production, lipid peroxidation and cytoplasmic leakage were also assessed., Results: The most active ethyl acetate extract (EA) showed potent inhibitory effect against S. mutans (0.390 μg/μl). TLC-bioautography indicated spots F1 & F2 to show inhibition zones. F1 was identified as kaempferol. This is the first report on flowers of B. ciliata against oral infection. The mode of action of F1 can be attributed to its ability to destroy the membrane integrity, reducing and disrupting biofilm. It also produced ROS within the bacterial cell, leading to lipid peroxidation and subsequently causing death of the bacteria., Conclusion: Kaempferol is the active compound in bioactive spot F1 which showed antibacterial and antibiofilm activity. The antibacterial activity can be linked with the membrane disrupting properties of kaempferol and producing ROS inside S. mutans. Thus, phytochemicals derived from B. ciliata can be used in the development of pharmaceutical dental products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Picrorhiza kurroa Royle ex Benth. ( P. kurroa /PK/Kutki), a Himalayan herb belonging to the family Scrophulariaceae, is widely known for its hepatoprotective activity. Traditionally, it is found to be effective for upper respiratory tract disorders, kidney and liver problems, dyspepsia and chronic diarrhoea but the mechanism of action is unclear. In this study, the mode of action of P. kurroa for the treatment of diabetic nephropathy (DN) was investigated by network pharmacology, molecular docking and in vitro assays. Numerous databases have been screened and 33 P. kurroa bioactive compounds and 56 targets were identified. The compounds-targets network, targets-pathways network and compounds-targets-pathways network were constructed. The major bioactive compounds include picrorhizaoside D, scrophuloside A, vanillic acid, arvenin I, cinnamic acid, picein, 6-feruloyl catalpol, picroside V, pikuroside, apocynin, picroside I, picroside IV, androsin, cucurbitacin P, boschnaloside, kutkoside, cucurbitacin O, cucurbitacin K, picracin, etc. The potential protein targets identified in this study were MMP1, PRKCA, MMP7, IL18, IL1, TNF, ACE, ASC, CASP1, NLRP3, MAP, KURROA1, mitogen-activated protein kinase (MAPK)14 and MAPK8. In the Database for annotation visualization and integrated discovery (DAVID) pathways and Gene Ontology enrichment analysis, 14 major DN signalling pathways were identified, including MAPK, renin-angiotensin system (RAS), TNF, signal transducer and activator of transcription (JAK-STAT), TLR, vascular endothelial growth factor (VEGF), mTOR, Wnt, Ras, PPARs, NFB, NOD and phosphatidylinositol signalling pathways. A molecular docking study revealed that 32 bioactive compounds of P. kurroa interacted with 14 significant proteins/genes associated with DN. P. kurroa extract was proven to enhance the survival rate of HEK cells significantly. Protein expression analysis using Western blot demonstrated that P. kurroa extract significantly altered the expression of p47phox, p67phox, gp91phox, IL-1 and TGFβ-1. As a result of network pharmacology and docking work, new concepts for discovering bioactive compounds and effective modes of action could be developed. The potential effect of P. kurroa extract on DN disease was evident in the in-vitro studies aided by network pharmacology and molecular docking.Communicated by Ramaswamy H. Sarma.

Farnesol (FAR) is a sesquiterpene molecule with high lipophilicity that has antibacterial and other pharmacological properties along with broad nutritional values with high commercial values. Although having potential, FAR stability behavior and degradation kinetics are not available in the literature. Hence, it is very essential to develop a simple, rapid, accurate, precise, robust, cheap UHPLC-DAD method for FAR. It was also proposed to study mechanistic insights into FAR under different degradation conditions. Therefore, we hypothesized to do systematic stability studies along with degradation kinetic and accelerated stability studies. The developed method was validated. FAR was studied for stress studies, degradation kinetics and ADMET prediction of degradants. Degradation products were characterized using LC-QTOF-ESI-MS. Developed method consists of an isocratic mobile phase with a wavelength of 215 nm. The percent recoveries for FAR were observed within the acceptance limit of 98-102%. The eight major degradation products were formed during stress studies. FAR follows first-order degradation kinetics. FAR and all degradants were found to have more than 75% good human oral absorption, and are non-toxic. FAR UHPLC-DAD method was developed, validated and performed stability studies to know the possible degradation pattern along with degradation kinetic studies., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Andrographis paniculata (Burm. f.) Nees and Andrographis nallamalayana J.L.Ellis have traditionally been used to treat various ailments such as mouth ulcers, intermittent fever, inflammation, snake bite. This study compares the comparative in vitro cytotoxic activity, and phytochemical profiling of methanol extract of A. nallamalayana (ANM) and A. paniculata (APM). UPLC-ESI-QTOF-MS/MS analysis has been performed. The cytotoxic activity of crude methanol extracts were evaluated against three different cancer cell lines (HCT 116, HepG2, and A549 cell line). Both plants' extract exhibited significant cytotoxic activity against tested cell lines in a dose-dependent manner. IC 50 of ANM and APM in HCT 116 cell was 11.71 ± 2.48 μg ml -1 and 45.32 ± 0.86 μg ml -1 and in HepG2 cell line was 15.65 ± 2.25 μg ml -1 and 60.32 ± 1.05 μg ml -1 respectively. Cytotoxicity of these two extracts was comparatively similar in A549 cells. ANM induced cytotoxicity involved programmed cell death, externalisation of phosphatidylserine, ROS generation, up-regulation and down-regulation of major apoptotic markers. HRMS analysis of ANM and APM resulted in the identification of 59 and 42 compounds, respectively. Further, using the MS/MS fragmentation approach, 20 compounds, of which 18 compounds were identified for the first time from ANM, which belongs to phenolic acids, flavonoids, and their glycosides. Three known compounds, echioidinin, skullcapflavone I and 5,2',6'-trihydroxy-7-methoxyflavone 2'- O -β-d-glucopyranoside, were isolated from A. nallamalayana and their crystal structures were reported for the first time. Subsequently, seven major compounds were identified in A. nallamalayana by direct comparison (retention time and UV-spectra) with authentic commercial standards and isolated compounds using HPLC-UV analysis. The cytotoxicity of phytochemicals from both the plants using in silico tools also justify their in vitro cytotoxic activity. It is the first report on the comparative characterisation of phytochemicals present in the methanolic extract of both the species of Andrographis , along with the cytotoxic activity of A. nallamalayana ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Prostate cancer (PCa) is a major cause of mortality and morbidity in men. Available therapies yield limited outcome. We explored anti-PCa activity in a polyphenol-rich fraction of Bergenia ligulata (PFBL), a plant used in Indian traditional and folk medicine for its anti-inflammatory and antineoplastic properties. PFBL constituted of about fifteen different compounds as per LCMS analysis induced apoptotic death in both androgen-dependent LNCaP and androgen-refractory PC3 and DU145 cells with little effect on NKE and WI38 cells. Further investigation revealed that PFBL mediates its function through upregulating ROS production by enhanced catalytic activity of Monoamine oxidase A (MAO-A). Notably, the differential inactivation of NRF2-antioxidant response pathway by PFBL resulted in death in PC3 versus NKE cells involving GSK-3β activity facilitated by AKT inhibition. PFBL efficiently reduced the PC3-tumor xenograft in NOD-SCID mice alone and in synergy with Paclitaxel. Tumor tissues in PFBL-treated mice showed upregulation of similar mechanism of cell death as observed in isolated PC3 cells i.e., elevation of MAO-A catalytic activity, ROS production accompanied by activation of β-TrCP-GSK-3β axis of NRF2 degradation. Blood counts, liver, and splenocyte sensitivity analyses justified the PFBL safety in the healthy mice. To our knowledge this is the first report of an activity that crippled NRF2 activation both in vitro and in vivo in response to MAO-A activation. Results of this study suggest the development of a novel treatment protocol utilizing PFBL to improve therapeutic outcome for patients with aggressive PCa which claims hundreds of thousands of lives each year., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Medicinal plant-based therapies can be important for treatment of cancer owing to high efficiency, low cost and minimal side effects. Here, we report the anti-cancer efficacy of Ricinus communis L. fruit extract (RCFE) using estrogen positive MCF-7 and highly aggressive, triple negative MDA-MB-231 breast cancer cells. RCFE induced cytotoxicity in these cells in dose and time-dependent manner. It also demonstrated robust anti-metastatic activity as it significantly inhibited migration, adhesion, invasion and expression of matrix metalloproteinases (MMPs) 2 and 9 in both cell lines. Further, flow cytometry analysis suggested RCFE-mediated induction of apoptosis in these cells. This was supported by attenuation of anti-apoptotic Bcl-2, induction of pro-apoptotic Bax and caspase-7 expressions as well as PARP cleavage upon RCFE treatment. RCFE (0.5 mg/Kg body weight) treatment led to significant reduction in tumor volume in 4T1 syngeneic mouse model. HPLC and ESI-MS analysis of active ethyl acetate fraction of RCFE detected four compounds, Ricinine, p-Coumaric acid, Epigallocatechin and Ricinoleic acid. Individually these compounds showed cytotoxic and migration-inhibitory activities. Overall, this study for the first time demonstrates the anti-cancer efficacy of the fruit extract of common castor plant which can be proposed as a potent candidate for the treatment of breast cancer.

Background & Objective: Nitrogen mustard derivatives form one of the major classes of anti-cancer agents in USFDA approved drugs list. These are polyfunctional alkylating agents which are distinguished by a unique mechanism of adduct formation with DNA involving cross-linking between guanine N-7 of one strand of DNA with the other. The generated cross-linking is irreversible and leads to cell apoptosis. Hence it is of great interest to explore this class of anticancer alkylating agents., Methods: An exhaustive list of reviews, research articles, patents, books, patient information leaflets, and orange book is presented and the contents related to nitrogen mustard anti-cancer agents have been reviewed. Attempts are made to present synthesis schemes in a simplified manner. The mechanism of action of the drugs and their side effects are also systematically elaborated., Results: This review provides a platform for understanding all aspects of such drugs right from synthesis to their mechanism of action and side effects, and lists USFDA approved ANDA players among alkylating anticancer agents in the current market., Conclusion: Perusing this article, generic scientists will be able to access literature information in this domain easily to gain insight into the nitrogen mustard alkylating agents for further ANDA development. It will help the scientific and research community to continue their pursuit for the design of newer and novel heterocyclic alkylating agents of this class in the coming future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Orcinol glucoside (OG) - loaded nanostructured lipid carrier (NLC), coated with polyethylene glycol-25/55-stearate (PEG-25/55-SA), were explored for delivering OG to improve in vitro cytotoxicity against gastrointestinal tract (GIT), colon and hepatoma carcinoma cell lines. It is being expected that the PEGylated formulations would possess the sustainability in withstanding the adverse physiological extremities like the most significant metabolic activities and phase I / II enzymatic activities in the intestines., Methods: NLCs were prepared using tristearin, oleic acid and PEG-25/55-stearate by hot homogenization-ultrasonic dispersion; characterized by DLS, TEM, SEM, AFM, entrapment efficiency and drug loading capacity studies., Results: NLC diameter ranged from 160 to 230 nm with negative zeta potential of -8 to -20 mV. TEM/SEM and AFM studies suggest spherical and smooth surface morphologies. Differential scanning calorimetry studies reveal the loss of crystallinity when OG was incorporated into the NLC. NLCs showed initial burst release, followed by sustained release of OG. PEG-NLC exhibited superior anticancer activity against GIT and also in hepatoma cancer cell lines., Conclusions: This is the first report demonstrating a practical approach for possible oral delivery of OG in GIT and targeting hepatoma cancer, warranting further in vivo studies for superior management of GIT cancer.

A series of N-substituted amide linked triazolyl β-d-glucopyranoside derivatives (4a-l) were synthesized and their in vitro inhibitory activity against yeast α-glucosidase enzyme [EC.3.2.1.20] was assessed. Compounds 4e (IC 50 =156.06μM), 4f (IC 50 =147.94μM), 4k (IC 50 =127.71μM) and 4l (IC 50 =121.33μM) were identified as the most potent inhibitors for α-glucosidase as compared to acarbose (IC 50 =130.98μM) under the same in vitro experimental conditions. Kinetic study showed that both 4e and 4f inhibit the enzyme in a competitive manner with p-nitrophenyl α-d-glucopyranoside as substrate. Molecular docking studies of 4e, 4f, 4k and 4l were also carried out using homology model of α-glucosidase to find out the binding modes responsible for the inhibitory activity. This study revealed that the binding affinity of compounds 4e, 4f, 4k and 4l for α-glucosidase were -8.2, -8.6, -8.3 and -8.5kcal/mol respectively, compared to that of acarbose (-8.9kcal/mol). The results suggest that the N-substituted amide linked triazole glycoconjugates can reasonably mimic the substrates for the yeast α-glucosidase., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A number of 2-methyl-4-(2-oxo-2-phenyl-ethyl)-5-phenyl-furan-3-carboxylic acid alkyl ester derivatives (3a-j) were synthesized and evaluated for their in vitro inhibitory activity on soybean lipoxygenase enzyme. Among the screened compounds, 5-(4-bromo-phenyl)-4-[2-(4-bromo-phenyl)-2-oxo-ethyl]-2-methyl-furan-3-carboxylic acid methyl ester (3g) has been found to exhibit potent inhibitory activity with IC 50 12.8μM using nordihydroguaiaretic acid (NDGA) as standard. Molecular modeling was employed for better understanding of the binding between compounds and soybean lipoxygenase enzyme. The predicted binding energy values correlated well with the observed in vitro data., (Copyright © 2017 Elsevier Inc. All rights reserved.)