Unveiling the chemical profiling and remarkable modulation of carbohydrate metabolism by costus root, Dolomiaea costus (Falc.) in streptozotocin (STZ)-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dolomiaea costus (Falc.), formerly Saussurea costus (Falc.) Lipsch., an ayurvedic medicinal plant, has long been recognized and utilized in diverse indigenous systems of medicine for its multifaceted therapeutic properties, including anti-inflammatory, carminative, expectorant, antiarthritic, antiseptic, aphrodisiac, anodyne, and antidiabetic effects. AIM OF THE STUDY: The potential and underlying mechanisms of D. costus root as an antidiabetic agent were investigated in this study. Additionally, the quantification of phenolic and flavonoid compounds, which dominate the extracts, was of particular interest in order to elucidate their contribution to the observed effects. MATERIALS AND METHODS: High-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was employed to analyze the chemical constituents in D. costus root aqueous extract (DCA) and D. costus root ethanolic extract (DCE). Furthermore, the inhibitory potentials of DCE and its respective fractions as well as DCA against α-amylase, α-glucosidase, and lipase enzymes were assessed. Subsequently, the efficacy of DCA and DCE extracts was evaluated using an established streptozotocin (STZ)-induced diabetic animal model; this involved administering the extracts at doses of 200 and 400 mg/kg bwt. and comparing them with a positive control (glibenclamide (Glib.) at 0.6 mg/kg bwt.). After induction of diabetes (except for negative control), all animals received the treatments orally for 21 days consecutively, followed by the collection of rat serum to assess various parameters including, glycemic and lipid profiles, liver and kidney functions, antioxidant activity, glycolysis, and gluconeogenesis pathways. RESULTS: The results of HPLC-ESI-MS/MS revealed that isochlorogenic acid A (8393.64 µg/g) and chlorogenic acid (6532.65 µg/g) were the predominant compounds in DCE and DCA, respectively. Both extracts exhibited notable antidiabetic properties, as evidenced by their ability to regulate blood glycemic and lipid profiles (glucose, insulin, HBA1C; HDL, TC, TGs), liver enzymes (ALT, ALP, AST), kidney function (urea, creatinine, uric acid), oxidative stress biomarkers (MDA), antioxidant enzymes (CAT, GSH, SOD), as well as glycolysis (glucokinase) and gluconeogenesis (G-6-P, FBP1) pathways. CONCLUSIONS: Furthermore, the administration of D. costus extracts significantly mitigated STZ-induced diabetic hyperglycemia. These results can be attributed, at least partially, to the presence of several polyphenolic compounds with potent antioxidant and anti-inflammatory activities.

Costus spiralis extract restores kidney function in cisplatin-induced nephrotoxicity model: Ethnopharmacological use, chemical and toxicological investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Costus spiralis (Jacq.). Roscoe (Costaceae) is traditionally used in Brazil for the treatment of kidney diseases such as pyelonephritis, urethra inflammation, kidney stones, and inflammatory conditions. There are reports of its use by Brazilian Indians since the 17th century when it was known as "pacocatinga." Currently, the use of the Costus species in Brazil is widespread, which was evidenced by the inclusion of the genus in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS). AIM OF THE STUDY: This study aimed to confirm the ethnopharmacological use of Costus spiralis in the treatment of kidney diseases, toxicity study using animal models, and the phytochemistry of the species. MATERIALS AND METHODS: The chemical profile of Costus spiralis leaves extract (CSLE) was obtained for the hydroethanolic extract by ultra-performance liquid chromatography coupled to a mass spectrometer and ultraviolet detector with diode array (UPLC-UV/DAD-ESI-MS). The acute oral toxicity of the extract was predicted using the neutral red uptake cytotoxicity assay. Wistar rats were used in a model in vivo for confirmation of acute oral toxicity (2000 mg/kg p.o. for 14 days.) and determination of the effect on a cisplatin-induced nephrotoxicity model. RESULTS: The analysis by UPLC-UV/DAD-ESI-MS showed that the chemical composition of the extract is mostly di-glycosylated flavones of apigenin. In the extract were identified the flavones vicenin II and schaftoside. The quantification of total flavonoids by spectrometry showed 0.880%. CSLE proved to be safe for acute oral administration (2000 mg/kg) with an IC50 value of 222.9 µg/mL and predicted oral toxic dose of 523.82 µg/mL in a neutral red uptake cytotoxicity assay. The absence of death allows the classification of the extract in class 5 according to OECD 423 guidelines and therefore it can be considered as a high acute safety product, which is highly relevant, considering the wide popular use of the species. In the cisplatin-induced nephrotoxicity model, C. spiralis extract (5, 15, and 30 mg/kg) significantly improved renal function, reversing almost completely the effects on plasma creatinine levels and creatinine clearance (p < 0.001). CONCLUSIONS: This study demonstrates that oral administration of Costus spiralis extract leaves is safe and effective in restoring the renal function in rats in a cisplatin-induced nephrotoxicity. It is suggested that the observed activity is related to the flavonoids present. This hypothesis should be confirmed, and the participation of other secondary metabolites should be investigated in the future.

Costus speciosus extract protects against the oxidative damage of zearalenone via modulation of inflammatory cytokines, Nrf2 and iNOS gene expression in rats.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin that induces severe health disturbances in humans and animals. This study aimed to determine the bioactive compounds in Costus speciosus extract (CSE) using GC-MS and evaluate its protective capability against ZEN-induced oxidative damage, genotoxicity, and cytotoxicity in rats. Six groups of male Sprague Dawley rats were treated orally for 15 days including the control group, CSE-treated groups at low (200 mg/kg b. w) or high (400 mg/kg b. w) dose, ZEN-treated group (40 µg/kg b. w), and the groups treated with ZEN plus the low or the high dose of CSE. Blood and tissue samples were collected for different assays and pathological analyses. The results of GC-MS indicated the identification of 6 compounds and Azulene was the major. Animals that received ZEN showed severe disturbances in serum biochemical, cytokines, oxidative stress indicators, mRNA expression of iNOS, Nrf2, and inflammatory-related genes. ZEN also increased micronucleated polychromatic erythrocytes (MNPCEs) and comet tail formation in bone marrow cells along with the disturbances in the histological architecture of the liver and kidney. Co-administration of CSE plus ZEN could normalize the majority of the tested parameters and the histological picture at a dose as low as 200 mg/kg b. w. Therefore, CSE protects against ZEN toxicity via its antioxidant activity, modulation of iNOS, inflammatory-related genes, and the Nrf2 pathway and it could be used in the endemic regions.

Nanoparticles of Costus speciosus Ameliorate Diabetes-Induced Structural Changes in Rat Prostate through Mediating the Pro-Inflammatory Cytokines IL 6, IL1ß and TNF-α.

Diabetes mellitus is a common global health problem. Among the complications that are frequently associated with DM are the alternation of sexual function and fertility, especially in young men. This study aimed to assess the efficacy of nanoparticles of Costus speciosus (C. speciosus) in preserving the prostatic structure of diabetic rats and to explore the mechanism behind this effect. A model of DM was induced in male albino rats by a single intraperitoneally injection of streptozotocin (STZ, 60 mg/kg body weight). Five groups (n = 10 each) of rats were included in this study: the control, C. speciosus gold nanoparticles-treated (150 mg/kg body weight through gastric intubation for 30 days), untreated diabetic, metformin-treated diabetic (500 mg/kg/day gastric intubation for 30 days) and the C. speciosus-treated diabetic group. The blood glucose, insulin and testosterone levels as well as oxidants/antioxidants status were assessed in the serum. Gene expression of proinflammatory cytokines TNF-α, IL1ß and IL-6 were assessed in the prostate homogenate. At the end of the experiment, the rats were sacrificed and the prostate was dissected out and prepared for histopathological and immunohistochemistry study using Ki67 and Bcl-2. C. Speciosus nanoparticles significantly decreased (p = 0.03) the blood glucose level while significantly increasing insulin (p = 0.01) and testosterone (p = 0.04) levels compared to the untreated diabetic rats. Oxidants/antioxidants status was markedly improved after administration of C. speciosus. Prostatic expression of the mRNA of pro-inflammatory cytokines IL-6, IL1ß and TNF-α was down-regulated in metformin- and C. speciosus-treated rats. The histological structure of the ventral prostate was preserved in metformin- and C. speciosus-treated diabetic rats with a significantly thicker epithelial cell layer and significant increase immunoexpression in Bcl-2 and Ki67. In conclusion, the protective effect induced by C. speciosus nanoparticles on the prostate of diabetic rats might be directly mediated through the down-regulation of inflammatory cytokines and the up-regulation of antioxidant activity and indirectly mediated through the anti-hyperglycemic effect through enhancing insulin secretion.

Adverse effect of rheumatoid arthritis on male Wistar rat's fertility: protective role of Costus extract.

Rheumatoid arthritis (RA) is a systemic autoimmune complaint. Advanced treatments resort to the traditional herbal therapy. The aim of this study is to assess the protective effect of Costus extract on the fertility of male rats with Freund's adjuvant-induced rheumatoid arthritis. Thirty male adult Wistar rats (190-200 g) were divided into six groups. They were subdivided into three groups; group I was the control group that received distilled water, and groups II and III received two various doses of Costus extract (200 and 400 mg/kg, respectively) for 60 days. Another three groups were subjected to RA induction via Freund's adjuvant. Rats were injected a dose of 0.1 ml of Freund's complete adjuvant (FCA) in the planter area of the left hind paw and then subdivided into 3 groups. Group I of RA-induced rats were given distilled water. The other two groups were given orally (200 and 400 mg/kg dosage of extract, respectively) from the 2nd day of RA induction for 60 days. Sex organ relative weight, sperm concentration assay, testicular histopathology and immunohistochemistry of androgen receptors, TNF α, and BAX protein were determined. The results showed that RA caused a significant decrease in the relative weight of sex organs and sperm count, which were relatively improved by doses of Costus (200, 400 mg/kg). RA induction caused testicular degeneration which markedly enhanced with Costus treatment as shown in histopathological sections. RA caused a reduction in %IHC of androgen receptors and increased expression level of both TNF α and BAX protein. Using IHC, it was revealed that RA caused a reduction in the expression level of androgen receptors and an increase in the expression of both TNF α and BAX protein. We can conclude that Costus speciosus had a potentially valuable role in improving fertility disorders caused by RA.

Increased insulin and GLUT2 gene expression and elevated glucokinase activity in ß-like cells of islets of langerhans differentiated from human haematopoietic stem cells on treatment with Costus igneus leaf extract.

In the quest to understand lost ß-cells regeneration in the diabetic condition, we have demonstrated successful differentiation of human haematopoietic stem cells (HSCs) to functional ß-like cells. Costus igneus (Ci) leaf extract is known to exhibit anti-diabetic properties by lowering the blood glucose level as demonstrated in mice models. To establish the anti-diabetic properties of Ci leaf extract on human subjects, we studied the effect of Ci on these differentiated ß-like cells. Ci leaf extract showed its anti-diabetic property through elevated glucokinase activity which catalyzes the rate-limiting step of glucose catabolism in ß-like cells and acts as a sensor for insulin production while decreasing the glucose-6-phosphatase activity. Upon increasing the concentrations of Ci leaf extract (25, 65, 105, 145, 185 µg/ml) and glucose concentrations (5.5, 11.1, and 25 mM) Ci leaf extract treated ß-like cells showed enhanced glucokinase and decreased glucose-6-phosphatase activities and an exponential rise in gene expressions of INS and GLUT2 was observed. The present study shows enhanced INS and GLUT2 gene expression and elevated glucokinase activity in ß-like cells differentiated from HSCs upon treatment with Ci leaf extract explain the anti-diabetic property of Ci leaf extract. This extract can be effectively used in the management of diabetes.

Influence of Soil Variation on Diosgenin Content Profile in Costus speciosus from Indo-Gangetic Plains.

Costus speciosus is a rich source of commercially important compound Diosgenin, distributed in different regions of India. The present investigation was aimed to quantify diosgenin through High Performance Thin Layer Chromatography in 34 germplasms of Costus speciosus and also to identify the superior sources and to correlate the macronutrients of rhizospheric soil. The starch content varied in microscopic examination and correlated inversely (r=-0.266) with diosgenin content. Findings revealed that the extraction process with acid hydrolysis yielded higher diosgenin content (0.15-1.88 %) as compared to non-hydrolysis (0.009-0.368 %) procedure. Germplasms from Uttar Pradesh (NBCS-4), Jharkhand (NBCS-39) and Bihar (NBCS-2) were identified as elite chemotypes based on hierarchical clustering analysis. The phosphorous content of respective rhizospheric soil correlated positively (r=0.742) with diosgenin content. Findings of present study are useful to identify the new agrotechniques. The elite germplasms can also be used as quality planting material for large scale cultivation in order to assure a sustained supply to the herbal drug industry.

The Estimation of the Anti-neurotoxic Effect of Costus Ethanolic Extract against Bifenthrin-Intoxication in Male Rats.

BACKGROUND AND OBJECTIVE: Pyrethroidsare a group of synthetic pesticides similar to the natural pesticide pyrethrum, which is produced by chrysanthemum flowers. Bifenthrin is one of the pyrethroids that are widely used pesticide in households and to control crop vectors. The main goal of this work was to investigate the possible ameliorating effect of Costus Ethanolic Extract (CEE) against neurotoxicity induced by bifenthrin in adult-male rats. MATERIALS AND METHODS: Rats were arranged randomly to 4 groups (8 rats each) as next. Group 1) control rats orally received 0.5 mL water for consecutive 30 days; group 2) healthy rats orally received CEE (200 mg kg) for consecutive thirty days; group 3) rats treated orally with 7 mg kg-1 day-1 bifenthrin for consecutive 30 days and group 4) included rats treated with bifenthrin for consecutive 30 days followed by administration with CEE another consecutive 30 days. RESULTS: The results showed that CEE succeeded to decline the neurotoxicity-induced by bifenthrin; this was evidenced by the significant reduction in TNF-α, IL- 1ß, MDA and nitric oxide levels in cortex, hippocampus and striatum concomitant with marked improvement in the values of GSH, dopamine, serotonin, AChE-ase, SOD, GPx and catalase that were diminished by bifenthrin intoxication. CEE improved also cognitive impairment and the deficits in motor coordination induced by bifenthrin. CONCLUSION: CEE was found successful, to a great extent, to counteract the bifenthrin-induced brain oxidative stress and neurochemical deteriorations and possesses a protective potential against brain-induced neurotoxicity. Therefore, it may be a promising supplement for the amelioration of BF-neurotoxicity.

Can Costus afer be used for co-treatment of COVID-19, its symptoms and comorbidities? A novel approach for combating the pandemic and implications for sub-Saharan Africa.

Despite the huge loss of lives and massive disruption of the world economy by the COVID -19 pandemic caused by SARS -CoV-2, scientists are yet to come out with an effective therapeutic against this viral disease . Several vaccines have obtained 'emergency approval ', but difficulties are being faced in the even distribution of vaccines amongst high- and low- income countries . On top of it, comorbidities associated with COVID -19 like diabetes, hypertension and malaria can seriously impede the treatment of the main disease, thus increasing the fatality rate . This is more so in the context of sub -Saharan African and south Asian countries . Our objective was to demonstrate that a single plant containing different phytoconstituents may be used for treatment of COVID -19 and comorbidities . Towards initial selection of a plant, existing scientific literature was scanned for reported relevant traditional uses, phytochemicals and pharmacological activities of a number of plants and their phytoconstituents pertaining to treatment of COVID-19 symptoms and comorbidities. Molecular docking studies were then performed with phytochemicals of the selected plant and SARS-CoV-2 components - Mpro, and spike protein receptor binding domain and hACE2 interface using AutoDock V ina. We showed that crude extracts of an indigenous African plant, Costus afer having traditional antidiabetic and antimalarial uses, has phytochemicals with high binding affinities for Mpro, and /or spike protein receptor binding domain and hACE2 interface; the various phytochemicals with predicted high binding energies include aferoside C, dibutyl phthalate, nerolidol, suginal, and ± -terpinene, making them potential therapeutics for COVID -19. The results suggest that crude extracts and phytochemicals of C. afer can function as a treatment modality for COVID -19 and comorbidities like especially diabetes and malaria .

Nephroprotective and antilithiatic activities of Costus spicatus (Jacq.) Sw.: Ethnopharmacological investigation of a species from the Dourados region, Mato Grosso do Sul State, Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Costus spicatus (Jacq.) Sw., also known as "cana-do-brejo," is a species that is widely used in Brazilian traditional medicine for the treatment of kidney diseases. However, no studies have evaluated its nephroprotective and antilithiatic effects. AIM: To investigate nephroprotective and antilithiatic effects of C. spicatus in a preclinical model of acute kidney injury (AKI) and in vitro nephrolithiasis. MATERIALS AND METHODS: C. spicatus leaves were collected directly from the natural environment in the Dourados region, Mato Grosso do Sul State, Brazil. The ethanol-soluble fraction of C. spicatus (ESCS) was obtained by infusion. Phytochemical characterization was performed by liquid chromatography coupled to diode array detector and mass spectrometer (LC-DAD-MS). We assessed whether ESCS has acute or prolonged diuretic activity. The nephroprotective effects of ESCS were evaluated in a model of AKI that was induced by glycerol (10 ml/kg, intramuscularly) in Wistar rats. Different doses of ESCS (30, 100, and 300 mg/kg) were administered orally for 5 days before the induction of AKI. Urinary parameters were measured on days 1, 3, 5, and 7. Twenty-four hours after the last urine collection, blood samples were obtained for the biochemical analysis. Blood pressure levels, renal vascular reactivity, renal tissue redox status, and histopathological changes were measured. Antilithiatic effects were evaluated by in vitro crystallization. Calcium oxalate precipitation was induced by sodium oxalate in urine samples with ESCS at 0.05, 0.5, and 5 mg/ml. RESULTS: From LC-DAD-MS analyses, flavonoids, saponins and other phenolic compounds were determined in the composition of ESCS. Significant reductions of the excretion of urinary total protein, creatinine, sodium, and potassium were observed in the AKI group, with significant histopathological damage (swelling, vacuolization, necrosis, and inflammatory infiltration) in the proximal convoluted tubule. Treatment with ESCS exerted a significant nephroprotective effect by increasing the urinary excretion of total protein, urea, creatinine, sodium, potassium, calcium, and chloride. All of the groups that were treated with ESCS exhibited a reduction of histopathological lesions and significant modulation of the tissue redox state. We also observed a concentration-dependent effect of ESCS on the crystallization of urinary crystals, with reductions of the size and proportion of monohydrated crystals. CONCLUSION: The data suggest that C. spicatus has nephroprotective and antilithiatic effects, suggesting possible effectiveness in its traditional use.

Costus pictus D. Don leaf extract stimulates GLP-1 secretion from GLUTag L-cells and has cytoprotective effects in BRIN-BD11 ß-cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Costus pictus D. Don, commonly known as insulin plant, is a traditional Indian antidiabetic herbal medicine with glucose-lowering and insulin secretory effects having been reported in animal models and humans with Type 2 diabetes. However, its effects on GLP-1 secretion from intestinal endocrine L-cells and potential metabolic and protective effects in insulin secreting pancreatic ß-cells are not yet fully understood. AIM OF THE STUDY: This study is aimed to elucidate the effects of Costus pictus D. Don leaf extract (CPE) on L-cell function and GLP-1 secretion using the established murine GLUTag L-cell model and to investigate its potential cytoprotective effects against detrimental effects of palmitate and cytokines in pancreatic ß-cells using BRIN-BD11 cells. METHODS: Costus pictus D. Don dried leaf powder was extracted by soxhlet method. Cell viability was determined by MTT assay. Changes in gene and protein expression were quantified by qPCR and western blotting, respectively. GLP-1 and insulin secretion were measured by ELISA. RESULTS: CPE significantly enhanced the percentage of viable BRIN-BD11 and GLUTag cells and protected BRIN-BD11 cells against palmitate- and proinflammatory cytokine-induced toxicity. CPE enhanced acute GLP-1 secretion 6.4-16.3-fold from GLUTag cells at both low (1.1 mM) and high (16.7 mM) glucose (P < 0.01) concentrations. Antioxidant (Nrf2, Cat & Gpx1) and pro-proliferative (Erk1 and Jnk1) gene expression were upregulated by 24 h culture with CPE, while proinflammatory transcription factor NF-κB was downregulated. CONCLUSION: Diminished postprandial GLP-1 secretion and loss of insulin secreting ß-cells are known contributors of T2DM. Our data suggests that CPE acutely stimulates GLP-1 secretion from L-cells. Long term exposure of the BRIN-BD11 cells to CPE enhances cell number and may protect against palmitate and proinflammatory cytokines by activating multiple pathways. Thus, the current study suggests that the possible antidiabetic properties of CPE may be linked to enhanced GLP-1 secretion and ß-cell protection which could be beneficial in the management of T2DM.

Costus afer leaf extract protects against testicle damage caused by cyclosporine A in adult male Wistar rats through an antioxidant mechanism.

Cyclosporine A is one of the most widely used drugs in organ transplant and oncology patients. But its use is accompanied by many toxicities. This study aimed to investigate the possible protective effect of Costus afer (C. afer) leaf extract on cyclosporine A-induced testicular toxicity. This study was carried out on 40 adult male Wistar rats were divided into four groups: control, C. afer, cyclosporine A and cyclosporine A+ C. afer groups. The investigations include genital weight, sperm count and characters, serum luteinising hormone (LH) and testosterone, testicular tissue contents of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) and lipid peroxidation (MDA). Besides, a histopathological examination of testicular tissue stained with haematoxylin and eosin (H & E) was performed. Cyclosporine A+ C. afer group showed a significant increase in the genital weight, serum testosterone, sperm count, motility and viability. Besides, the extract significantly decreased testicular content of MDA and increased SOD, CAT and GSHPx. C. afer coadministration significantly decreased serum LH and sperm abnormalities and protected against testicular histopathological alterations. The extract showed a protective effect against testicular toxicity associated with cyclosporine A and that was through an antioxidant mechanism.

High dose of standardised extract of Costus afer leaves potentiates cadmium reproductive toxicity in Wistar rats.

Protective effects of standardised extract of Costus afer leaves (CAME), an extract with good antioxidants on cadmium-induced reproductive toxicity in male rats, were investigated in this study. Forty-two adult male Wistar rats were randomly divided into six groups and were treated every day regularly for 4 weeks. G1 (control) rats received 1 ml of vehicle treatment. G2 rats were intoxicated with 2.5 mg kg-1  day-1 s.c cadmium chloride for 1 week. G3 and G4 rats were intoxicated with cadmium as in G2 rats and were treated orally with 100 and 200 mg/kg bwt/day of CAME, respectively, for 4 weeks. Group G5 and G6 rats were orally treated with 100 and 200 mg kg-1  day-1 bwt of CAME, respectively, for 4 weeks. Significant changes (p < 0.05) in andrological parameters (sperm count, sperm morphology, serum testosterone and nitric oxide concentration) and testicular antioxidant parameters (reduced glutathione, lipid peroxidation and activities of catalase, glutathione S-transferase and glutathione peroxidase) caused by Cd toxicity were improved in cadmium-intoxicated rats treated with 100 mg/kg body weight of CAME. Administration of 200 mg/kg body weight of CAME to cadmium-intoxicated rats potentiated reproductive toxic effects of cadmium. In conclusion, lower dose of CAME is preferred over high dose in treatment of cadmium-induced reproductive toxicity in rats.

Synthesis of ZnO nanoparticles using insulin-rich leaf extract: Anti-diabetic, antibiofilm and anti-oxidant properties.

Here, we report the novel fabrication of ZnO nanoparticles using the Costus igneus leaf extract. Gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy to determine the bioactive components present in the plant extract. The synthesis of Ci-ZnO NPs (C. igneus- coated zinc oxide nanoparticles) was accomplished using a cost-effective and simple technique. Ci-ZnO NPs were specified using UV-visible spectroscopy, FTIR, XRD, and TEM. Ci-ZnO NPs was authenticated by UV-Vis and exhibited a peak at 365 nm. The XRD spectra proved the crystalline character of the Ci-ZnO NPs synthesized as hexagonal wurtzite. The FTIR spectrum illustrated the presence of possible functional groups present in Ci-ZnO NPs. The TEM micrograph showed evidence of the presence of a hexagonal organization with a size of 26.55 nm typical of Ci-ZnO NPs. The α-amylase and α-glucosidase inhibition assays demonstrated antidiabetic activity of Ci-ZnO NPs (74 % and 82 %, respectively), and the DPPH [2,2-diphenyl-1-picrylhydrazyl hydrate] assay demonstrated the antioxidant activity of the nanoparticles (75%) at a concentration of 100 µg/ml. The Ci-ZnO NPs exhibited promising antibacterial and biofilm inhibition activity against the pathogenic bacteria Streptococcus mutans, Lysinibacillus fusiformis, Proteus vulgaris, and Vibrio parahaemolyticus. Additionally, the Ci-ZnO NPs showed biocompatibility with mammalian RBCs with minimum hemolytic activity (0.633 % ±â€¯0.005 %) at a concentration of 200 µg/ml.

The protective effect of Costus afer Ker Gawl aqueous leaf extract on lead-induced reproductive changes in male albino Wistar rats.

INTRODUCTION: Lead is a multiple organ toxicant and an oxidative-stress inducer. The effect of Costus afer on metal- induced male reprotoxicity has not been previously carried out, hence this study. The present study investigates the protective effect of Costus afer aqueous leave extract on lead- induced reproductive damages in male albino Wistar rats. METHODS: Adult male albino Wistar rats were weighed and separated into five groups of five rats each. Groups 1 & 2 served as normal and toxic controls receiving deionized and leaded (CH3COO)2Pb.3H2O and water respectively. Groups 3, 4 and 5 were given 750, 1500 and 2250mg/kg of Costus afer orally, respectively while receiving Pb2+ water ad libitum for 28 days. RESULTS: The reproductive and antioxidant parameters obtained from the result served as scientific evidence in the study. The result showed non-significant changes in the absolute and relative weights of epididymis and testes in the Pb Group versus the control. Significant increases were recorded in the sperm analysis, blood lead (7.9±1.02; 1.1±0.01) level (BLL), luteinizing hormone (LH) (8.5±1.4:5.5±0.4), and a decrease in follicle stimulating hormone (FSH) (4.5±2.6:6.5±1.65), with non-significant changes in testosterone (TET) (1.3±0.00:1.6±0.2) in the Pb group compared to the control. CONCLUSION: The treatment with Costus afer exhibited dose-dependent significant changes in testicular oxidative stress, hormonal, sperm analysis and histopathological changes induced by lead. Aqueous leaves extract of Costus afer may be protective against lead induced testicular damage.

Characterization of potent antidiabetic compounds from Costus pictus D. Don found in Assam, India using in vitro in vivo methods / Caracterización de compuestos antidiabéticos potentes de Costus pictus D. Don encontrados en Assam, India usando métodos in vitro e in vivo

Objective: Costus pictus D. Don is a traditionally used plant in Naojan area of Golaghat district of Assam, India specifically for treating diabetes. Six compounds were isolated from standardized methanolic extract of the aerial parts (MECP). The prime objective was to select most potent antidiabetic compounds among the isolated compounds viz. F67, F12, F16, F3032, F37 & F48 by using in vitro and in vivo methods. Methods: Isolated compounds were subjected to initial screening by in vitro alfa-amylase inhibition activity assay using iodine-starch and DNSA (3,5-dinitrosalicylic acid) methods. Compounds depicting promising in vitro activity were selected for in vivo Streptozotocin (STZ) induced antidiabetic screening activity. Then based on the in vivo results, most potent compounds were selected for instrumental characterization by Q-TOF ESI-MS, 1HNMR, 13CNMR & FTIR. Results: Amongst the six compounds isolated from MECP, three compounds viz. F12, F16 & F48 showed potent in vitro activity. They were subsequently subjected to evaluation of the antidiabetic activity in vivo by oral administration, at dose of 10, 20 & 50 mg/kg body weight respectively, using Wister rat (120-150 g) and Glibenclamide (10mg/k body weight) as standard. Two compounds, F12 and F48 at dose of 50 mg/kg body weight, reversed STZ induced diabetic parameters (increased blood glucose level, altered plasma profile and histoarchitecture of the pancreatic and hepatic cells) with statistical significance (P<0.05), that was comparable with the standard. Hence, instrumental characterization by Q-TOF ESI-MS, 1HNMR, 13CNMR & FTIR of compounds F12 and F48 isolated from MECP was carried out which established their identity as (3,5,7-Trihydroxy-3'-hydroxy-4'-methoxy) flavanone or [3,5,7-Trihydroxy-2-(3'-hydroxy-4'-methoxy phenyl)-2,3-dihydrochromen-4-one] and 3,5,8-trihydroxy-7-methoxy-2-phenyl-2,3-dihydrochromen-4-one or [7-methoxy-3, 5, 8 trihydroxy flavanone] respectively. Conclusion: The study culminated in elucidation of two flavanones as most potent compounds in exhibiting antidiabetic activities. The findings were thus successful in validating the traditional practices in Golaghat district of Assam, India, associated with the use of Costus pictus D. Don in the treatment of diabetes

Objetivo: Costus pictus D. Don es una planta usada tradicionalmente en la zona del distrito de Golaghat Naojan de Assam, India específicamente para el tratamiento de la diabetes. Seis compuestos se aislaron a partir de extracto metanólico estandarizados de las hojas (MECP). El principal objetivo fue seleccionar compuestos antidiabéticos más potentes entre los compuestos aislados viz. F67, F12, F16, F3032, F37 y F48 mediante métodos in vitro e in vivo. Métodos: Los compuestos aislados fueron sometidos a cribado inicial mediante ensayo de actividad de inhibición in vitro alfa-amilasa utilizando yodo-almidón y métodos DNSA (ácido 3,5-dinitrosalicilico). Los compuestos que presentaban una actividad in vitro prometedora se seleccionaron para la actividad de cribado antidiabético inducida por estreptozotocina (STZ) in vivo. En función de los resultados in vivo, la mayoría de los compuestos potentes se seleccionaron para la caracterización instrumental por Q-TOF ESI-MS, 1HNMR, 13CNMR y FTIR. Resultados: Entre los seis compuestos aislados de MECP, tres compuestos viz. F12, F16 y F48 mostraron una potente actividad. Posteriormente se sometieron a evaluación de la actividad antidiabética in vivo mediante administración oral, en dosis de 10, 20 y 50 mg / kg peso, utilizando ratas Wister (120-150 g) y glibenclamida (10 mg / kg peso) como estándar. Dos compuestos, F12 y F48 en dosis de 50 mg/kg peso, revirtieron los parámetros diabéticos inducidos por STZ (aumento del nivel de glucosa en sangre, plasma perfil alterado y histoarquitectura del páncreas y células hepáticas), con significación estadística (P<0,05) que era comparable con la norma. Se llevo a cabo la caracterización instrumental por Q-TOF ESI-MS, RMN 1H, RMN 13C y FTIR de los compuestos F12 y F48 aislado de MECP, lo que estableció su identidad como (3,5,7-trihidroxi-3'-hidroxi-4'- metoxi) flavanona o [3,5,7-trihidroxi-2- (fenil 3'-hidroxi-4'-metoxi) -2,3-dihydrochromen-4-ona] y 3,5,8-trihidroxi-7-metoxi -2-fenil-2,3-dihydrochromen-4-ona o [7-metoxi-3, 5, 8 trihidroxi flavanona] respectivamente. Conclusión: El estudio culminó en la elucidación de dos flavanonas como los compuestos más potentes en la exposición de actividades antidiabéticas. Los resultados lograron validar las prácticas tradicionales en el distrito de Golaghat de Assam, India, asociados con el uso de Costus pictus D. Don en el tratamiento de la diabetes

Antioxidant and antihyperlipidemic activity of Costus speciosus against atherogenic diet-induced hyperlipidemia in rabbits.

OBJECTIVE: An extract of Costus speciosus (CSE), a herb widely used in folk medicine, was evaluated for its antioxidant, antihyperlipidemic and ameliorating effects on histopathological changes in atherogenic rabbits. METHODS: Twenty-four male rabbits (Oryctolagus cuniculus) were divided into 4 groups. Three groups were fed a diet containing 3% saturated fat and 1.3% cholesterol for 40 d. One of these was sacrificed on the 40th day and was called the pathogenic (P) group; the other two groups received treatment for another 30 d as follows: one received 0.8 g/(kg·d) of CSE and the other was given 0.01 g/(kg·d) of simvastatin. The normal group was sacrificed on the 70th day and used as a control. RESULTS: CSE showed radical-scavenging ability. Administration of CSE for a 30-day period resulted in a significant decrease in total cholesterol, triacylglycerol, low-density lipoprotein and aspartate aminotransferase compared to the P group, while levels of hemoglobin, packed corpuscular volume and red blood cells were elevated. With respect to studies performed on the heart, a decrease in malondialdehyde and an increase in reduced glutathione were noted. Total protein increased in the liver, heart and aorta after treatment with CSE and also a marked improvement in histopathological parameters was demonstrated. CONCLUSION: The present findings indicate that the C. speciosus rhizome possesses antiatherogenic and antioxidant properties which may provide protective effects against oxidative stress in atherosclerotic rabbits.

Antimicrobial, antiquorum sensing, and antiproliferative activities of sesquiterpenes from Costus speciosus rhizomes.

The quorum sensing inhibitory (QSI) and antimicrobial potentials of the total methanol extract (TME) and different extractives as well as the sesquiterpenes: dehydrodihydrocostus lactone (1), dehydrocostus lactone (2), arbusculin A (3), santamarine (4), reynosin (5), and specioic acid (6) isolated from Costus speciosus rhizomes were evaluated. The CHCl3:EtOAc (1:1), EtOAc, and TME fractions exhibited potent antibacterial activity toward B. cereus with inhibition zone diameter 13 mm. While the CHCl3 fraction showed strong activity towards S. aureus and B. cereus with inhibition zone diameter 11 and 19 mm, respectively. Moreover, the TME and CHCl3 fractions have strong activity towards C. albicans with inhibition zone diameter 15 and 12 mm, respectively. Compound 5 showed prominent activity towards B. cereus (MIC 385 µg/mL). However, 6 exhibited significant activity with MIC values of 150, 400, and 550 µg/mL towards S. aureus, E. coli, and B. cereus, respectively. Moreover, it showed potent antifungal effect towards C. albicans (MIC 320 µg/mL). Most of the tested fractions had QSI activity against C. violaceum. Only compound 6 exhibited moderate QSI effect with disappearance of violet pigment. In addition, compounds 1-6 were evaluated for their in vitro antiproliferative activity towards KB, BT-549, SK-MEL, and SKOV-3 cancer cell lines.

Effect of Costus spiralis (Jacq.) Roscoe Leaves, Methanolic Extract and Guaijaverin on Blood Glucose and Lipid Levels in a Type II Diabetic Rat Model.

This study aimed to isolate and identify flavonoids with hypoglycemic activity in Costus spiralis leaves. The methanolic extract (ME) was rich in flavonoids, while the powdered leaves (PL) contained considerable amounts of macro- and microelements. Oral acute treatment of streptozotocin (STZ)-induced diabetic rats for 18 h with the C. spiralis PL, ME and isolated guaijaverin (GUA) lowered glycemia, improved oral glucose tolerance and inhibited liver lipid peroxidation. GUA and ME lowered plasma levels of low-density and non-high density lipoproteins; GUA also lowered total cholesterol levels. PL, ME and GUA did not significantly alter the plasma levels of triglycerides, high-density lipoproteins, very low-density lipoproteins, creatinine and aspartate transaminase, and the total protein levels in the kidney and liver tissues. Therefore, C. spiralis leaves are promising raw materials and rich sources of bioactive flavonoids for the development of novel antidiabetic drugs due to their hypoglycemic, antidyslipidemic and antioxidant actions.

Potential synergistic effects of quercetin with other phytoconstituents of Costus pictus (insulin plant) extract in the control of hyperglycemia and prevention of NSAID-induced gastroenteropathy in diabetic rats.

There is a need of multifactorial management to treat T2DM. Till date, no clinically simulated animal model and therapy for NSAID-induced gastroenteropathic damage (NSAID-iGD) in T2DM patients. T2DM was developed using high-fat diet plus multiple low doses of streptozotocin (30 mg/kg, IP). Rats treated with ethanolic extract of Insulin plant (EIP; 125, 250 and 500 mg/kg, PO; b.i.d.)/Quercetin (QCT; 50 mg/kg)/vehicle for total 10 days. Diclofenac sodium (DCF; 7.5 mg/kg, PO, b.i.d.) administered for final five days of EIP/vehicle administration. Rats fasted after last dose on the 9th day; water was provided ad libitum. 12 h after the last dose on 10th day, GI tracts assessed for haemorrhagic damage, XO activity, LPO, intestinal permeability, luminal pH alterations along with haematological, biochemical and histological parameters. The evidence suggested that DCF administration caused significant gastroenteropathic damage. In presence of T2DM, NSAID-iGD significantly exacerbated. Whereas, QCT/EIP treatment significantly attenuated T2DM dependent exacerbation of NSAID-iGD, and also efficiently managed T2DM in a dose-dependent manner. Low amount of QCT in EIP(190.96 ±â€¯7.5 ng/mg) than its effective dose(50 mg/kg) indicates that EIP's other phytoconstituents (e.g. Kaempferol, Ascorbic acid, Lupeol, Diosgenin, ß-sitosterol, Stigmasterol, ß-amyrin, etc.) giving synergistic actions. Costus pictus/QCT has potential to be promising candidate to treat patient with T2DM and NSAID-gastroenteropathy in T2DM.