Chemometric profiling and anti-arthritic activity of aerial parts of Glinus oppositifolius (L.) Aug. DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Glinus oppositifolius (L.) Aug. DC. belongs to the family Molluginaceae, an annual prostrate herb traditionally used to treat inflammations, arthritis, malarial, wounds, fevers, diarrhoea, cancer, stomach discomfort, jaundice, and intestinal parasites. However, the anti-arthritic activity of the aerial part has still not been reported. AIM OF THE STUDY: To investigate the antioxidant and anti-arthritic activity of G. oppositifolius in Complete Freund's Adjuvant (CFA) induced rats. MATERIALS AND METHODS: The dried aerial parts of this plant material were defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The in vitro anti-arthritic activity of methanolic extract of G. oppositifolius (MEGO) was evaluated in protein denaturation, membrane stabilization, and inhibition of proteinase assay at 25, 50, 100, 200, and 400 µg/ml concentrations. Female Wistar rats were immunized sub-dermally into the right hind paw with 0.1 ml of CFA. Rats were administered with MEGO at doses of 200 and 400 mg/kg once daily for fourteen days after arthritis induction. Assessment of arthritis was performed by measuring paw diameter, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters, followed by the analysis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1-beta (IL-1ß), cyclooxygenase-2 (COX-2), interleukin 13 (IL-13) and interleukin 10 (IL-10) and histopathological study. In vivo antioxidant effect was investigated in enzymatic assays. The presence of phytoconstituents was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. In silico molecular docking study of the compounds was carried out against COX-2, IL-1ß, IL-6, and TNF-α using AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. RESULTS: MEGO's in vitro anti-arthritic activity showed dose-dependent inhibition of protein denaturation, membrane stabilization, and proteinase inhibition, followed by significant in vivo anti-arthritic activity. The rats treated with MEGO showed tremendous potential in managing arthritis-like symptoms by restoring hematological, biochemical, and histological changes in CFA-induced rats. MEGO (200 and 400 mg/kg) showed a significant alleviation in the levels of hyper expressed inflammatory mediators (TNF-α, IL-1ß, and IL-6) and oxidative stress (SOD, CAT, GSH, and LPO) in CFA-induced rats. Spergulagenin-A as identified by LC-MS analysis, exhibited the highest binding affinity against COX-2 (-8.6), IL-1ß (7.2 kcal/mol), IL-6 (-7.4 kcal/mol), and TNF-α (-6.5 kcal/mol). CONCLUSIONS: Provided with the comprehensive investigation, methanolic extract of G. oppositifolius against arthritic-like condition is a proof of concept that revalidates its ethnic claim. The presence of Spergulagenin-A might be responsible for the anti-arthritic activity.

In-silico, in-vitro and in-vivo Biological Activities of Flavonoids for the Management of Type 2 Diabetes.

In spite of the fact that many medicinal plants have been truly utilized for the management of diabetes all through the world, very few of them have been reported scientifically. Recently, a diverse variety of animal models have been established to better understand the pathophysiology of diabetes mellitus, and new medications to treat the condition have been introduced in the market. Flavonoids are naturally occurring substances that can be found in plants and various foods and may have health benefits in the treatment of neuropathic pain. Flavonoids have also been shown to have an anti-inflammatory impact that is significant to neuropathic pain, as indicated by a decrease in several pro-inflammatory mediators such TNF-, NF-B IL-6, and IL-1. Flavonoids appear to be a viable novel therapy option for macrovasular complications in preclinical models; however, human clinical data is still inadequate. Recently, several in silico, in-vitro and in-vivo aproaches were made to evaluate mechanisms associated with the pathogenesis of diabetes in a better way. Screening of natural antidiabetic agents from plant sources can be analysed by utilizing advanced in-vitro techniques and animal models. Natural compounds, mostly derived from plants, have been studied in diabetes models generated by chemical agents in the majority of research. The aim of this work was to review the available in silico, in-vitro and animal models of diabetes for screening of natural antidiabetic agents. This review contributes to the scientist's design of new methodologies for the development of novel therapeutic agents having potential antihyperglycemic activity.

Recent Advances in Chemical Composition and Transdermal Delivery Systems for Topical Bio-actives in Skin Cancer.

Skin cancer, including basal cell carcinoma, melanoma, and squamous cell carcinoma, is conventionally treated by surgery, phototherapy, immunotherapy, and chemotherapy. For decades, surgical removal of malignant cancers has favored patients' therapeutic options. However, multiple aspects, such as the patient's comorbidities, the anatomical location of the lesion, and possible resistance to recurrent excisions, can influence the decision to conduct surgery. Therefore, topical and transdermal therapy may be a more appropriate option, allowing for higher therapeutic levels at the site of action and reducing toxicity than systemic therapy. The most commonly used topical agents for treating skin carcinoma are- 5-fluorouracil, imiquimod, sonidegib, dacarbazine, etc. However, physicochemical drug characteristics and skin physiological barriers limit the anticancer potency of topical as well as transdermal drug delivery. In recent years, unquestionable signs of progress have been demonstrated to circumvent these challenges. In particular, significant studies have been made, including modification of bio-actives, permeability enhancers, incorporation of advanced nano and microcarriers, and physical enhancement devices. This critical review summarizes the advancement in the chemical composition of bioactives used in skin cancer, such as sinecatechins, BIL-010t, patidegib, gingerol, curcumin, remetinostat, epigallocatechin-3-gallate, etc. Furthermore, this review specifically addresses the progress in transdermal delivery systems for melanoma and nonmelanoma cancer therapy, emphasizing advances in physical and chemical penetration enhancement and nanocarrier-assisted transdermal systems.

Current Treatment Strategies Against Multidrug-Resistant Bacteria: A Review.

There are several bacteria called superbugs that are resistant to multiple antibiotics which can be life threatening specially for critically ill and hospitalized patients. This article provides up-to-date treatment strategies employed against some major superbugs, like methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Escherichia coli. The pathogen-directed therapeutics decrease the toxicity of bacteria by altering their virulence factors by specific processes. On the other hand, the host-directed therapeutics limits these superbugs by modulating immune cells, enhancing host cell functions, and modifying disease pathology. Several new antibiotics against the global priority superbugs are coming to the market or are in the clinical development phase. Medicinal plants possessing potent secondary metabolites can play a key role in the treatment against these superbugs. Nanotechnology has also emerged as a promising option for combatting them. There is urgent need to continuously figure out the best possible treatment strategy against these superbugs as resistance can also be developed against the new and upcoming antibiotics in future. Rational use of antibiotics and maintenance of proper hygiene must be practiced among patients.

Antitumor activity and antioxidant property of Curcuma caesia against Ehrlich's ascites carcinoma bearing mice.

CONTEXT: Curcuma caesia Roxb. (Zingiberaceae), commonly known as "Kala Haldi" in Bengali, has been traditionally used for the treatment of cancer, bruises, inflammation and as an aphrodisiac. OBJECTIVE: To evaluate the antitumor activity and antioxidant status of the methanol extract of Curcuma caesia (MECC) rhizomes on Ehrlich's ascites carcinoma (EAC)-treated mice. MATERIALS AND METHODS: In vitro cytotoxicity assay of MECC was evaluated by using Trypan blue method. Determination of in vivo antitumor activity was performed after 24 h of EAC cells (2 × 10(6) cells/mouse) inoculation; MECC (50 and 100 mg/kg i.p.) was administered daily for nine consecutive days. On day 10, half of the mice were sacrificed and the rest were kept alive for assessment of increase in lifespan. Antitumor effect of MECC was assessed by the study of tumor volume, tumor weight, viable and non-viable cell count, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes. RESULTS: MECC showed direct cytotoxicity (IC50 90.70 ± 8.37 µg/mL) on EAC cell line. MECC exhibited significant (p < 0.01) decrease in tumor volume, tumor weight, viable cell count and percentage increased the lifespan (57.14 and 88.09%) of EAC-treated mice. Hematological profile, biochemical estimation, tissue antioxidant assay significantly (p < 0.01) reverted to normal level in MECC-treated mice. CONCLUSION: MECC possesses potent antitumor activity that may be due to its direct cytotoxic effect or antioxidant properties. Further research is in progress to find out the active principle(s) of MECC for its antitumor activity.

Antitumor activity and antioxidant role of Streblus asper bark against Ehrlich ascites carcinoma in Swiss albino mice.

The present study assessed the methanol extract of Streblus asper stem bark (MESA) for antitumor effect and antioxidant influence against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Twenty four hours after intraperitonial inoculation of tumor (EAC) cells in mice, MESA was administered at 200 and 400 mg/kg body weight daily for 9 consecutive days. On the 10 th day, half of the mice were sacrificed for estimation of tumor parameters, haematological, liver and kidney antioxidant parameters; and the rest were kept alive for assessment of survival. MESA exhibited dose dependent and significant (p < 0.01) decrease in tumor proliferation and extended the life span of EAC bearing mice. Hematological profiles were significantly (p < 0.01) restored near to normal in MESA treated mice as compared to EAC control. MESA treatment significantly (p < 0.01) modulated the hepatic and renal antioxidant parameters as compared to EAC control. The present study demonstrated that S. asper bark possessed promising antitumor efficacy in mice, plausibly mediated by amelioration of oxidative stress by multiple mechanisms.

Evaluation of antitumor activity of Mimusops elengi leaves on Ehrlich's ascites carcinoma-treated mice.

CONTEXT: Mimusops elengi (M. elengi) Linn. (Sapotaceae) has been used as a folk medicine in wound healing, and the treatment of pain, and inflammation in many parts of India. OBJECTIVE: The purpose of this investigation was to explore the antitumor activity of methanol extract of M. elengi (MEME) in Swiss albino mice against Ehrlich ascites carcinoma (EAC) cell line. MATERIALS AND METHODS: Twenty-four hours after intraperitoneal (i.p.) inoculation of tumor (EAC) cells in mice (n = 12), MEME was administered at 200 and 300 mg/kg body weight daily for 9 consecutive days. On day 10, half of the mice were dissected and the rest were kept alive for assessment of increase in life span. The antitumor effect of MEME was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameter, and biochemical estimations. In vivo antioxidant parameters were assayed by estimating liver tissue enzyme. In vitro cytotoxicity assay of MEME was measured by using trypan blue exclusion method. RESULTS AND DISCUSSION: MEME showed significant (p < .001) decrease in tumor volume, packed cell volume, and viable cell count, and increased the life span of EAC bearing mice. Hematological, biochemical profile, and in vivo antioxidant parameters were significantly restored toward normal levels in MEME-treated mice as compared to EAC control. MEME also showed direct cytotoxicity on EAC cell line in a dose-dependent manner. CONCLUSIONS: The present study demonstrates that M. elengi leaves exhibited antitumor activity in Swiss mice, which may be due to its cytotoxic effect and antioxidant properties.

Evaluation of antitumor activity and in vivo antioxidant status of Anthocephalus cadamba on Ehrlich ascites carcinoma treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Anthocephalus cadamba (Roxb.) Miq. (Family: Rubiaceae) is commonly known as "Kadamba" in Sanskrit and Hindi in India. Various parts of this plant have been used as a folk medicine for the treatment of tumor, wound healing, inflammation and as a hypoglycemic agent. AIM OF STUDY: The purpose of this investigation was to evaluate the antitumor activity and antioxidant status of defatted methanol extract of A. cadamba (MEAC) on Ehrlich ascites carcinoma (EAC) treated mice. MATERIALS AND METHODS: In vitro cytotoxicity assay has been evaluated by using the trypan blue method. The determination of in vivo antitumor activity was performed by using different EAC cells (2 × 10(6) cells, i.p.) inoculated mice groups (n=12). The groups were treated for 9 consecutive days with MEAC at the doses of 200 and 400 mg/kg b.w. respectively. After 24h of last dose and 18 h of fasting, half of the mice were sacrificed and the rest were kept alive for assessment of increase in life span. The antitumor potential of MEAC was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes. RESULTS: MEAC showed direct cytotoxicity on EAC cell line in a dose dependant manner. MEAC exhibited significant (P<0.01) decrease in the tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. The hematological profile, biochemical estimations and tissue antioxidant assay were reverted to normal level in MEAC treated mice. CONCLUSION: Experimental results revealed that MEAC possesses potent antitumor and antioxidant properties. Further research is going on to find out the active principle(s) of MEAC for better understanding of mechanism of its antitumor and antioxidant activity.

Antihyperglycemic activity and antioxidant role of Terminalia arjuna leaf in streptozotocin-induced diabetic rats.

CONTEXT: Terminalia arjuna Roxb. (Combretaceae), commonly known as Arjuna, is a large tree grown throughout the Indian peninsula and used traditionally for several medicinal purposes. OBJECTIVE: To evaluate antihyperglycemic and antioxidant role of methanol extract of T. arjuna leaf (META) in Wistar rats. MATERIALS AND METHODS: Hyperglycemia was induced in rats by single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight). Three days after STZ induction, the hyperglycemic rats were treated with META orally at the dose of 100 and 200 mg/kg body weight daily for 15 days. Glibenclamide (0.5 mg/kg, orally) was used as reference drug. The fasting blood glucose levels were measured on every fifth day during the 15-day treatment. Serum biochemical parameters such as serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), cholesterol, and total protein were estimated. Antioxidant properties were assessed by estimating hepatic lipid peroxidation, reduced glutathione (GSH), and catalase (CAT). RESULTS AND DISCUSSION: META at the dose of 100 and 200 mg/kg orally significantly (P < 0.001) and dose-dependently reduced and normalized blood glucose levels as compared with that of STZ control group. Serum biochemical parameters were significantly (P < 0.001) restored toward normal levels in META-treated rats as compared with STZ control. META treatment also significantly (P < 0.001) decreased lipid peroxidation and recovered GSH level and CAT activity toward normal as compared with STZ control. CONCLUSION: The present study infers that T. arjuna leaf demonstrated remarkable antihyperglycemic activity in STZ-induced diabetic rats. The potential antihyperglycemic action is plausibly due to its underlying antioxidant role.

Antitumor activity of Sansevieria roxburghiana rhizome against Ehrlich ascites carcinoma in mice.

CONTEXT: Sansevieria roxburghiana Schult. & Schult. f. (Agavaceae) is a herbaceous perennial plant traditionally used for coughs, rheumatism; as an expectorant, febrifuge, purgative, and tonic. OBJECTIVE: To evaluate the hydroalcoholic extract of S. roxburghiana rhizome (HASR) for antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. METHODS: Twenty-Four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, HASR was administered at 50 and 100 mg/kg body weight for nine consecutive days. On day 10 half of the mice were sacrificed and rest were kept alive for assessment of increase in life-span. The antitumor effect of HASR was assessed by evaluating tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life-span of EAC bearing hosts. Hematological profiles and serum biochemical parameters were estimated. Further, antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). RESULTS AND DISCUSSION: HASR showed a significant (p < 0.001) decrease in tumor volume, packed cell volume and viable cell count and increased the life span of EAC bearing mice. Hematological and serum biochemical profiles were restored to normal levels in HASR treated mice as compared to EAC control. HASR treatment significantly (p <0.001) decreased lipid peroxidation and recovered GSH, SOD and CAT towards normal as compared to EAC control. CONCLUSION: The present study demonstrates that S. roxburghiana rhizome exhibited remarkable antitumor activity in Swiss mice that is plausibly attributable to its augmenting endogenous antioxidant mechanisms.

Evaluation of anticancer activity of Cleome gynandra on Ehrlich's Ascites Carcinoma treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Cleome gynandra L. (Capparidaceae), is commonly known as 'Hurhur'and 'Karaila' in India and 'Cat's whiskers' in English. Traditionally the whole plant is used in the treatment of tumor, anti-inflammatory and lysosomal stability actions. AIM OF STUDY: The objective of present study is to explore the anticancer activity of the methanol extract of the Cleome gynandra in Swiss albino mice against Ehrlich Ascites Carcinoma (EAC) cell line. MATERIALS AND METHODS: Anticancer activity of methanol extract of Cleome gynandra (MECG) was evaluated in Swiss albino mice against Ehrlich Ascites Carcinoma (EAC) cell line at the doses of 200 and 400mg/kg body weight intraperitoneally. MECG was administered for nine consecutive days. Twenty-four hours of last dose and 18 h of fasting, the mice were sacrificed and antitumor effect of MECG assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight and hematological parameters of EAC bearing host. RESULTS: MECG showed significant decrease in (p<0.01) tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. Hematological profile such as RBC, hemoglobin, WBC and lymphocyte count reverted to normal level in MECG treated mice. CONCLUSION: From the result it was showed that the extract has potent dose dependent anticancer activity and that is comparable to that of 5-fluorouracil.