5H-benzo[c]fluorene derivative exhibits antiproliferative activity via microtubule destabilization.

Present study aimed at a single component cyclization of 2-benzylidene-1-tetralones for the preparation of 5H-benzo[c]fluorenes and their antiproliferative activity. This ring closure reaction underwent via reductive cyclization in the presence of a sodium borohydride-aluminium chloride system. Ten diverse 5H-benzo[c]fluorene derivatives were prepared and evaluated for antiproliferative activity against three human cancer cell lines by SRB assay. Four of these benzofluorenes exhibited significant antiproliferative effect with an IC50 < 10.75 µM. The best representative compound 21, exhibited IC50 against K562 leukemic cells at 3.27 µM in SRB assay and 7.68 µM in Soft agar colony assay. It exhibited a microtubule destabilization effect in tubulin kinetics and inhibited 82.9 % microtubule polymer mass at 10 µM concentration in Protein Sedimentation assay (Microtubule). Compound 21 exerted G0/G1 phase arrest in cell division cycle analysis in K562 cells. It also induced apoptosis in K562 cells via activation of Caspase cascade pathway. Furthermore, compound 21 also possessed anti-inflammatory activity by inhibiting TNF-α and IL-6 moderately. It exhibited significant in vivo efficacy and reduced K562 tumour in xenograft mice by 47 % at an 80 mg/kg oral dose. Further, it was found to be safe and well tolerable up to 1000 mg/kg in Swiss albino mice. Compound 21 needs to be optimized for better in vivo efficacy in rodent models for further development.

In-Vitro and In-Silico Studies of Brevifoliol Ester Analogues against Insulin Resistance Condition.

BACKGROUND: Brevifoliol is a diterpenoid that occurs naturally in the plants of Taxus genus and is widely used as chemotherapy agent for the management of cancer. A series of semisynthetic esters analogues of brevifoliol were prepared by Steglich esterification and attempted for their pharmacological potential against insulin resistance conditions using in-vitro and in-silico assays. OBJECTIVE: The aim of this study is to understand the pharmacological potential of eighteen semisynthetic analogs through Steglich esterification of Brevifoliol against insulin resistance condition Methods: In the in-vitro study, insulin resistance condition was induced in skeletal muscle cells using TNF-α, pro-inflammatory cytokine and these cells were treated with brevifoliol analogues. The most potent analouge was further validated using in-silico docking study against the tumor necrosis factor (TNF-α) (PDB ID: 2AZ5) and Human Insulin Receptor (PDB ID: 1IR3), using the Auto dock Vina v0.8 program. RESULTS: Although, all the analogues of Brevifoliol significantly exhibited the pharmacological potential. Among all, analogue 17 was most potent in reversing the TNF-α induced insulin resistance condition in skeletal muscle cells and also to inhibit the production of TNF-α in LPSinduced inflammation in macrophage cells in a dose-dependent manner. Similarly, in-silico molecular docking studies revealed that analogue 17 possesses a more promising binding affinity than the selected control drug metformin toward the TNF-α and insulin receptor. CONCLUSION: These findings suggested the suitability of analogue 17 as a drug-like candidate for further investigation toward the management of insulin resistance conditions.

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.

Chemico-nutritional characterization and anti-inflammatory potential of Chirabilva (Holoptelea integrifolia Roxb.) seed: alternate source of protein supplement and fatty acids.

Exploring unconventional protein sources can be an alternative strategy to meet the deficiency. The seeds of Chirabilva (Holoptelea integrifolia Roxb., Family- Ulmaceae) are eaten raw by the ethnic communities of Southeast Asian countries. The present study assessed the chemical, nutritional, and biological potential of the seeds (HIS) and pericarp (HISP) of H. integrifolia. The seeds contain mainly fixed and very few essential oils. The fixed oil of HIS is composed primarily of unsaturated oleic (47%) and saturated palmitic (37%) acids. The HIS are exceptional due to a high content of lipid (50%), protein (24%), carbohydrates (19%), fiber (4%), and anti-nutritional components within permissible limits. The high content (in mg/Kg) of phosphorus (6000), magnesium (422), Calcium (279), and essential nutrients (Ni, Co, Zn, Fe, Cu, Mn, and Cr) in the range of (0.04-6.69) were observed. The moderate anti-oxidant potential of HISP was evident in single electron transfer in-vitro assays. Moreover, HISP extract and HIS solvent-extracted fixed oil showed anti-inflammatory action in lipopolysaccharide-induced HaCaT cells by significantly attenuating pro-inflammatory cytokines (TNF-α) without causing cytotoxicity. Results support de-oiled HIS cake as an alternative source of a high-protein diet and its oil with anti-inflammatory attributes for topical applications.

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.

Cooperative STAT3-NFkB signaling modulates mitochondrial dysfunction and metabolic profiling in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) continues to pose a significant health challenge and is often diagnosed at advanced stages. Metabolic reprogramming is a hallmark of many cancer types, including HCC and it involves alterations in various metabolic or nutrient-sensing pathways within liver cells to facilitate the rapid growth and progression of tumours. However, the role of STAT3-NFκB in metabolic reprogramming is still not clear. APPROACH AND RESULTS: Diethylnitrosamine (DEN) administered animals showed decreased body weight and elevated level of serum enzymes. Also, Transmission electron microscopy (TEM) analysis revealed ultrastructural alterations. Increased phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated nuclear factor kappa B (p-NFκß), dynamin related protein 1 (Drp-1) and alpha-fetoprotein (AFP) expression enhance the carcinogenicity as revealed in immunohistochemistry (IHC). The enzyme-linked immunosorbent assay (ELISA) concentration of IL-6 was found to be elevated in time dependent manner both in blood serum and liver tissue. Moreover, immunoblot analysis showed increased level of p-STAT3, p-NFκß and IL-6 stimulated the upregulation of mitophagy proteins such as Drp-1, Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK-1). Meanwhile, downregulation of Poly [ADP-ribose] polymerase 1 (PARP-1) and cleaved caspase 3 suppresses apoptosis and enhanced expression of AFP supports tumorigenesis. The mRNA level of STAT3 and Drp-1 was also found to be significantly increased. Furthermore, we performed high-field 800 MHz Nuclear Magnetic Resonance (NMR) based tissue and serum metabolomics analysis to identify metabolic signatures associated with the progression of liver cancer. The metabolomics findings revealed aberrant metabolic alterations in liver tissue and serum of 75th and 105th days of intervention groups in comparison to control, 15th and 45th days of intervention groups. Tissue metabolomics analysis revealed the accumulation of succinate in the liver tissue samples, whereas, serum metabolomics analysis revealed significantly decreased circulatory levels of ketone bodies (such as 3-hydroxybutyrate, acetate, acetone, etc.) and membrane metabolites suggesting activated ketolysis in advanced stages of liver cancer. CONCLUSION: STAT3-NFκß signaling axis has a significant role in mitochondrial dysfunction and metabolic alterations in the development of HCC.

Acyclic monoterpenoid-rich essential oil of Cymbopogon distans mitigates skin inflammation: a chemico-pharmacological study.

The topical application of essential oils is considered an effective treatment for skin diseases. Cymbopogon distans (Nees ex Steud.) Wats (Poaceae) is a promising aromatic grass widespread in the Himalayan temperate zone. Therefore, using in-vitro and in-vivo bioassays, we examined the chemical and pharmacological characteristics of essential oil hydro-distilled from C. distans coded as CDA-01, specifically concerning skin inflammation. Characterization using GC-FID and GC-MS provided a chemical fingerprint for CDA-01, enabling the identification of 54 compounds; amongst them, citral (34.3%), geranyl acetate (21.2%), and geraniol (16.4%) were the most abundant. To examine the anti-inflammatory potential, CDA-01 treatment on LPS-stimulated macrophage cells in addition to 12-O-tetradecanoylphorbol-13-acetate (TPA) generated cutaneous inflammatory reaction in the mouse ear was assessed through quantification of the inflammatory markers. Consequently, CDA-01 demonstrated protection against inflammation caused by LPS by lowering the pro-inflammatory cytokines (IL-6 and TNF-α) level in HaCaT cells with negligible cytotoxicity. Consistent with the in-vitro findings, CDA-01 treatment reduced pro-inflammatory mediators (TNF-, IL-6, and NO) and lipid peroxidation in an in-vivo investigation. Subcutaneous inflammation in TPA-treated mice ears was similarly decreased, as evidenced by the histological and morphological studies. As a result of our findings, it is possible that CDA-01 could be an effective treatment for skin inflammation disorders.

Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats.

Liquiritigenin (LTG) and its bioprecursor isoliquiritigenin(ISL), the main bioactives from roots of Glycyrrhiza genus are progressively documented as a potential pharmacological agent for the management of chronic diseases. The aim of this study was to evaluate the pharmacological potential of liquiritigenin, isoliquiritigenin rich extract of Glycyrrhiza glabra roots (IVT-21) against the production of pro-inflammatory cytokines from activated macrophages as well as further validated the efficacy in collagen-induced arthritis model in rats. We also performed the safety profile of IVT-21 using standard in-vitro and in-vivo assays. Results of this study revealed that the treatment of IVT-21 and its major bioactives (LTG, ISL) was able to reduce the production of pro-inflammatory cytokines (TNF-α, IL-6) in LPS-activated primary peritoneal macrophages in a dose-dependent manner compared with vehicle-alone treated cells without any cytotoxic effect on macrophages. In-vivo efficacy profile against collagen-induced arthritis in Rats revealed that oral administration of IVT-21 significantly reduced the arthritis index, arthritis score, inflammatory mediators level in serum. IVT-21 oral treatment is also able to reduce the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue and mRNA level of pro-inflammatory cytokines in paw tissue in a dose-dependent manner when compared with vehicle treated rats. Acute oral toxicity profile of IVT-21 demonstrated that it is safe up to 2000 mg/kg body weight in experimental mice. This result suggests the suitability of IVT-21 for further study in the management of arthritis and related complications.

Taxoids-rich extract from Taxus wallichiana alleviates high-fat diet-induced insulin resistance in C57BL/6 mice through inhibition of low-grade inflammation.

The needle powder of Taxus wallichiana is in use for the management of diabetes and inflammation-related complications in the Indian and Chinese Systems of Traditional Medicine but the lack of proper pharmacological intervention has prompted us to investigate the pharmacological mechanism against inflammation-induced insulin resistance in high-fat diet-fed C57BL/6 mice. Hexane (Tw-H), chloroform (Tw-C), and ethyl acetate (Tw-EA) extracts were prepared from a needle of T. wallichiana and its effect on glucose uptake against TNF-α-induced insulin resistance in skeletal muscle cells was studied. Among all, Tw-EA extract has shown promising glucose uptake potential. Tw-EA treatment is also able to decrease the lipid accumulation in adipocytes. Chemical signature of Tw-EA using HPLC showed the presence of taxoids. Efficacy of taxoids-rich extract from T. wallichiana (Tw-EA) was further validated in in vivo system against high-fat diet (HFD)-induced insulin resistance in C57BL/6 mice. Oral treatment of Tw-EA showed significant reduction in blood glucose, pro-inflammatory cytokine production and body weight gain when compared with vehicle-treated HFD-induced insulin resistance in C57BL/6 mice. Histopathology and immunohistochemistry study in skeletal muscle and adipose tissue revealed that oral treatment of Tw-EA is able to reduce the infiltration of inflammatory cells in skeletal muscles, ameliorate the hypertrophy in adipose tissue and upregulate the GLUT4 protein expression. Treatment with Tw-EA significantly up-regulated mRNA expression of insulin signaling pathway (IRS-1, PI3K, AKT, GLUT 4). This study suggested the beneficial effect of taxoids-rich extract from Taxus wallichiana against the inflammation-associated insulin resistance condition.

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.

Stimulation of glucose uptake by glycosides from Alectra parasitica subsp. chitrakutensis (M.A. Rau) K.K. Khanna & An. Kumar: An in-vitro study of TNF-α induced insulin resistance in L6 myoblasts.

Alectra parasitica subsp. chitrakutensis (M.A. Rau) K.K. Khanna & An. Kumar (Orobanchaceae) is a parasitic plant indigenous to India. Locally, the plant is known as 'Midaki and Nirgundikand'. It is used to treat fever, piles, cardiovascular disorders, and blood-borne non-infectious diseases by ethnic communities. The phytochemical investigation of A. parasitica subsp. chitrakutensis rhizome led to the isolation of azafrin (1), rehmaionoside-C (2), and mussaenoside (3). Compounds (2) and (3) are being reported for the first time from this plant. Compounds were evaluated for their intercellular glucose uptake activity in basal and insulin-TNF-α-stimulated L6 muscle cells. In particular, rehmaionoside C exhibited activity comparative to metformin, increasing uptake by basal- and insulin-TNF-α-stimulated cells by 4.88- and 3.90-fold and 5.04- and 4.04-fold. While azafrin and mussaenoside have produced 3.03- and 2.36-fold; 4.03- and 3.22-fold increase in intercellular glucose uptake. Compounds did not show toxicities in rat L6 myoblast cells. The study suggests that rehmaionoside-C from A. parasitica subsp. chitrakutensis might activate glucose uptake by insulin mimics and could be a nontoxic anti-diabetes lead for drug discovery.

p-Menthadienols-rich essential oil from Cymbopogon martini ameliorates skin inflammation.

Cymbopogon martini variety sofia, commonly known as ginger-grass, is an important aromatic crop used by the perfumery, medicinal and cosmetic industries worldwide. This study explores the chemical and possible pharmacological profile of hydro-distilled essential oil of C. martini variety sofia against skin inflammation. The essential oil extracted by the hydrodistillation process was analyzed by gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) to identify its constituents, and was coded as CMA-01 for further in vitro and in vivo pharmacological study related to skin inflammation. The chemical fingerprint revealed that CMA-01 oil has (E)-p-mentha-2,8-dien-1-ol (21.0%), (E)-p-mentha-1(7),8-dien-2-ol (18.1%), (Z)-p-mentha-1(7),8-dien-2-ol (17.4%), (Z)-p-mentha-2,8-dien-1-ol (9.0%), limonene (7.7%), and (E)-carveol (5.7%) as major components. The pre-treatment of CMA-01 showed significant inhibition of pro-inflammatory markers in activated HaCat cells without cytotoxic effect. The in vivo study revealed the ameliorative impact of CMA-01 against skin inflammation induced by TPA in mouse ears as evidenced by a reduction of ear edema, pro-inflammatory mediators (IL-6, TNF-α), oxidative stress markers (malondialdehyde and nitric-oxide) and histological changes in ear tissues without any skin irritation response on rabbit skin. These findings suggest the suitability of CMA-01 as a valuable therapeutic candidate for the treatment of skin inflammation.

An improved synthesis of indanocine and antiproliferative activity of 2-benzylindanocine via microtubule destabilization.

Indanocine, a potent anticancer investigational drug of National Cancer Institute-USA, has been much discussed in recent years. Present communication aimed at total synthesis of indanocine and its close analogues. Total synthesis was improved by double yields than previously reported yields. Some of the benzylidene and 2-benzyl derivatives with free rotation at C2 position exhibited potential cytotoxicities against various human cancer cell lines. Five such analogues exhibited potential antiproliferative effect against HCT-116 and MIA PACA-2 cell lines. Benzylindanocine 12i induced microtubule destabilization by occupying colchicine binding pocket of ß-tubulin. It also exhibited anti-inflammatory activity by down-regulating IL-6 and TNF-α. In Ehrlich ascites carcinoma model, 12i reduced 78.4% of EAC tumour in Swiss albino mice at 90 mg/kg (i.p.) dose. Further, in in vivo safety studies, 12i was found to be safe to rodents up to 1,000 mg/kg dose. Concomitant anticancer and anti-inflammatory activity of benzylindanocine is distinctive, which suggests its further optimization for better efficacy and druggability.

The Bioactive Potential of Culturable Fungal Endophytes Isolated From the Leaf of Catharanthus roseus (L.) G. Don.

INTRODUCTION: Endophyte is considered a source of natural bioactive secondary metabolites that provides an array of bioactive lead compounds. The present study was aimed to determine the antimicrobial and anti-inflammatory potential of fungal endophytes isolated from Catharanthus roseus. METHODS: A total of seven fungal endophytes crude extract were screened against bacterial pathogens. Of these, Curvularia geniculata CATDLF7 crude extract exhibited the most potent inhibitory activity against bacterial pathogens. Hence, CATDLF7 crude extract was subjected to chromatographic separation. This purification leads to the isolation of six pure compounds (1PS - 6PS). Of these, 3PS was found to be a major constituent and most effective against clinical isolates of methicillin- resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values ranging from 100 to 200 µg/ml. Based on the spectroscopic data, 3PS was characterized as α,ß- dehydrocurvularin. This compound also showed synergistic interaction with norfloxacin and reduced its MIC up to 32-folds with a fractional inhibitory concentration index (FICI) of 0.09. RESULTS: To understand the possible antibacterial mechanism of action, α,ß-dehydrocurvularin alone (100 µg/ml) exhibited efflux pump inhibitory potential by 0.84 fold decreasing in ethidium bromide (EtBr) fluorescence. In addition, α,ß-dehydrocurvularin inhibited inflammatory cytokines TNF-α and IL-6 production, which is further validated by molecular docking scores -4.921 and -5.641, respectively, for understanding orientation and binding affinity. CONCLUSION: Overall, the results highlighted identifying bioactive compound α,ß-dehydrocurvularin, which could be used as an antimicrobial and anti-inflammatory agent.

Hesperidin-rich ethanol extract from waste peels of Citrus limetta mitigates rheumatoid arthritis and related complications.

The aim of this study is to explore the possible pharmacological effects of fruit waste that may have a key role in converting the fruit waste into pharmaceutical agents. Citrus limetta (Rutaceae) is an important commercial citrus fruit crops used by juice processing industries. C. limetta peels are perishable waste material, which creates a big challenge in juice processing industries. Initial pharmaco-chemical profile of peels' extracts revealed that the ethanol extract (ClPs) has promising anti-inflammatory activity and rich in hesperidin content. In vivo experimental pharmacology profile of ClPs against arthritis and related complications revealed that oral administration of ClPs significantly reduced the arthritis score and arthritis index in elbow and knee joints against collagen-induced arthritis (CIA) in rats. Biochemical parameters include pro-inflammatory cytokines (TNF-α, IL-6, and IL-17A), and C-RP level in blood serum of CIA rats further confirmed the anti-arthritic profile of ClPs. Further individual experiments related to arthritis-related complications in experimental animals demonstrated the analgesic, anti-inflammatory, and antipyretic potential of ClPs in dose-dependent manner. The result of this study suggests the suitability of ClPs as a drug-like candidate for further investigation toward the management of arthritis and related complications.

A quinoline alkaloid rich Quisqualis indica floral extract enhances the bioactivity.

A volatile alkaloid quinoline-4-carbonitrile (QCN) was isolated from the floral extract of Quisqualis indica. Major compounds were trans-linalool oxide (1.0, 4.5%), methyl benzoate (1.0, 4.0%), 2,2,6-trimethyl-6-vinyl-tetrahydropyran-3-one (7.4, 17.8%), 2,2,6-trimethyl-6-vinyl-tetrahydropyran-3-ol (1.0, 1.2%), (E,E)-α-farnesene (29.1, 16.1%), QCN (5.7, 1.3%) in live and picked flowers, respectively. Flower compositions were altered due to change in enzymatic reaction at the time of picking. Some rearrangements of oxygenated terpenoids occurred in the process of hydrodistillation to obtain essential oil. Chemical synthesis of QCN and its selectively reduced products derived from QCN were prepared through green reaction process. The catalytic modification of QCN has produced quinoline-4-methylamine; the later compound has shown enhanced bio-activities. QCN and floral extract (absolute) have shown potential anti-inflammatory and antioxidant activities. Besides, floral absolute has shown significant anti-inflammatory and antioxidant activities due to improved QCN (19.7%) content to synergize amongst terpenoids and benzenoids as compared to the essential oil with 1.1% of QCN.

Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents.

A series of amide derivatives of stilbene was synthesized and investigated for osteogenic activity. Out of sixteen, seven compounds viz19c, 19g, 19i, 24b, 25a, 25c and 26a showed significant osteoblast differentiation within 1 pM-1 µM concentrations. Amongst all, 26a was identified as most active molecule which presented effective mineralization of osteoblasts and expression of mRNA of osteogenic marker gene such as BMP-2, ALP, and Runx-2 at 1 pM. In estrogen-deficient balb/c mice, 26a showed significant osteogenic activity at 5 mg-kg-1 body weight dose. The protein expression study for estrogen receptors α and ß (ER-α & ER-ß) using mouse calvarial osteoblasts (MCOs) and molecular docking analyses showed preferential expression of ER-ß by 26a indicating the possibility of ER-ß mediated osteogenic activity of 26a.

Microwave-assisted Single Step Cinnamic Acid Derivatization and Evaluation for Cytotoxic Potential.

BACKGROUND: Phenylpropylene biosynthesis pathway plays a crucial role in the vanillin and their derivative(s) production in the plants. The intermediate of vanillin synthesis i.e. cinnamic acid (CA) is converted into 2-Hydroxy 4-MethoxyBenzaldehyde (HMB) in Decalepis arayalpathra having a number of therapeutic value. OBJECTIVE: Microwave-assisted modifications in cinnamic acid were planned for potential anticancer properties with better yield and efficiency. The present study also confirms the presence of HMB and its precursor i.e. cinnamic acid in D. arayalpathra tubers. METHODS: We used a single step Microwave Assisted Synthesis (MAS) to modify cinnamic acid, and then examined the synthetic and natural cinnamic acid derivatives anticancer potential against six human cancer (K-562, WRL-68, A549, A431, MCF-7, and COLO-201) and two normal (L-132 and HEK-293) cell lines at 2, 10 and 50 µg/ml concentrations. RESULTS: ß-bromostyrene and ß -nitrostyrene have shown inhibition with IC50 values ranging 0.10-21 µM and 0.03-0.06 µM, respectively to the cancer cell lines. ß-bromostyrene was the most potent anticancer derivative of CA with better cellular safety and biocompatibility. CONCLUSION: The present study of microwave-assisted synthesis demonstrates a single-step modification in cinnamic acid. MAS is a fast, reliable, and robust method. The resultant compounds have shown in-vitro anticancer activity against human lung carcinoma and breast adenocarcinoma.

Aromatic ginger (Kaempferia galanga L.) extracts with ameliorative and protective potential as a functional food, beyond its flavor and nutritional benefits.

Aromatic ginger (Kaempferia galanga L) is native to India and believed to be originated in Burma. Despite substantial uses in a pickle and south-east Asian cuisines, aromatic ginger is chemically less studied than white and red ginger. Multi-directional investigations have been performed to evaluate chemical composition, nutritional values, ameliorative and protective potential of aromatic ginger (Kaempferia galanga) rhizome (KGR). Macro and micro components analysis confirmed that KGR contains protein, fiber, and high amount of essential minerals (potassium, phosphorous, and magnesium) along with appreciable amounts of iron, manganese, zinc, cobalt, and nickel. The anti-proliferative potential of KGR evaluated nine human cell lines. We have evaluated the anti-proliferative potential of hydrodistillate, extract, and key compound isolated from KGR on nine human cancer cell line and also reporting the safety to normal peritoneal macrophage cells. The current study demonstrates the anticancer potential of the KGR on MDA-MB-231 and WRL-68 cells. Very likely, results can be extrapolated to an animal or human system. Ethyl p-methoxy cinnamate (EPMC) was responsible for inhibiting the proliferation action which varied in a tested cell by intracellular reactive oxygen species (ROS) production. The present study demonstrates KGR as safe and high energy value medicinal spices with chemo-preventive action, without toxic phytochemicals, and tolerable other anti-nutritional factors.