Comprehensive Identification of Costus pictus Rhizome Extract as a Potent Plant Food: Unveiling Anti-Diabetic, Antimicrobial, Anticancer, and Anti-Inflammatory Properties.

Plant-derived foods are esteemed as natural preventives due to the constraints of contemporary pharmaceuticals, intensifying scrutiny of traditional medicinal flora. This study marked the first extensive evaluation of the anti-diabetic, anticancer, and anti-inflammatory effects of Costus pictus rhizomes, expanding beyond its well-known anti-diabetic properties in leaves. Hot air-dried C. pictus rhizomes underwent ultrasound-assisted extraction to produce the rhizome extract. Anti-diabetic effects were determined through enzymatic inhibition studies targeting "α-amylase and α-glucosidase," crucial enzymes in glucose regulation, revealing potent inhibitory effects with IC50 values of 266.591 and 324.938 µg/ml, respectively. The ubiquity of breast cancer and constrained therapeutic alternatives for triple negative breast cancer led to the utilization of the "MDA-MB 231 cell line" for the study. The rhizome extracts demonstrated cytotoxicity at an IC50 concentration of 770 µg/ml, with a pronounced decline in the "reactive oxygen species (ROS)" and "mitochondrial membrane potential (MMP)." They also regulated the cell cycle arrest at the G2/M phase and positively induced apoptosis, thus making it a potent anticancer candidate. Anti-inflammatory effects were assessed using "RAW 264.7 macrophage cell line" and exhibited dose-dependent reduction with IC50 of 495.074 µg/ml, declining nitric oxide (NO) levels. Antimicrobial studies provided insights into its effectiveness against pathogens. This pivotal understanding laid groundwork for advancing C. pictus rhizome extract as a potential ingredient in pharmaceuticals or functional foods, leading to favorable health outcomes.

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.

Metabolomic insights into the therapeutic mechanisms of costus (Saussurea costus (Falc.) Lipsch.) root extract in propylthiouracil-induced hypothyroidism rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea costus (Falc.) Lipschitz. is one of the most reputed medicinal plants as a traditional medicine in the Arab and Middle East regions in the treatment of thyroid disorders, however, more investigations are needed to fully understand its effectiveness and mechanism of action. AIM OF THE STUDY: The primary objective of the study was to assess the impact of Saussurea costus (COST) on the metabolic profiles of propylthiouracil (PTU)-induced hypothyroidism in rats. This involves a comprehensive examination of serum metabolites using UPLC/QqQ-MS analysis aiming to identify differential metabolites, elucidate underlying mechanisms, and evaluate the potential pharmacological effect of COST in restoring metabolic homeostasis. MATERIALS AND METHODS: Hypothyroidism was induced in female Sprague-Dawley rats by oral administration of propylthiouracil (PTU). UPLC/QqQ MS analysis of serum samples from normal, PTU, and PTU + COST rats was utilized for annotation of intrinsic metabolites with the aid of online Human metabolome database (HMDB) and extensive literature surfing. Multivariate statistical analyses, including orthogonal partial least squares discriminant analysis (OPLS-DA), discerned variations between the different groups. Serum levels of T3, T4 and TSH in addition to arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels in thyroid gland tissues; Phospholipase A2 group IIA (PLA2G2A), and lipoprotein lipase (LPL) in liver tissues were assessed by specific ELISA kits. Gene expression for key proteins of the primary evolved pathwayswere quantified by one-step qRT-PCR technique. Histopathological evaluation of thyroid gland tissue was performed by an investigator blinded to the experimental group using light microscope. RESULTS: Distinct clustering in multivariate statistical analysis models indicated significant variations in serum chemical profiles among normal, disease, and treated groups. VIP values guided the selection of differential metabolites, revealing significant changes in metabolite concentrations. Subsequent to COST treatment, 43 differential intrinsic metabolites exhibited a notable tendency to revert towards normal levels. Annotated metabolites, such as lysophosphatidylcholine (LPC), L-acetylcarnitine, gamma-glutamylserine, and others, showed differential regulation in response to PTU and subsequent S. costus treatment. Notably, 21 metabolites were associated with polyunsaturated fatty acids (PUFAs) biosynthesis, arachidonic acid (ARA) metabolism, and glycerophospholipid metabolism exhibited significant changes on conducting metabolic pathway analysis. CONCLUSIONS: COST improves PTU-induced hypothyroidism by regulating biosynthesis of PUFAs signified by n-3/n-6, ARA and glycerophospholipid metabolism. The study provides us a novel mechanism to explain the improvement of hypothyroidism and associated dyslipidemia by COST, depicts a metabolic profile of hypothyroidism, and gives us another point cut for further exploring the biomarkers and pathogenesis of hypothyroidism.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

BACKGROUND: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anti-cancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. OBJECTIVE: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. METHODS: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis. RESULTS: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. CONCLUSION: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Costus igneus, 'the Insulin plant' causing hypoglycaemia: Two case reports.

Costus igneus, commonly known as the 'Insulin plant' has been traditionally used in India to lower blood sugar levels. Its method of action is through a protein peculiar to itself, which has hypoglycaemic action. It therefore may prove harmful if used in excess, or together with other hypoglycaemic agents.

HPLC-ESI/MS-MS characterization of compounds in Dolomiaea costus extract and evaluation of cytotoxic and antiviral properties: molecular mechanisms underlying apoptosis-inducing effect on breast cancer.

BACKGROUND: Dolomiaea costus (syn: Saussurea costus; Family Asteraceae) occupies an important place in the traditional Chinese medicinal plants and is prescribed for a wide range of disorders. The current study aimed to tentatively identify the phytoconstituents of D. costus extract and to explore antiproliferative activity against human breast cancer cells and its possible apoptotic mechanism along with antiviral activity against human adenovirus 5 (Adv-5). METHODS: The phytoconstituents of 70% ethanol extract of D. costus were assessed using HPLC/ESI-MS/MS technique. The cell viability was investigated against breast cancer cell line (MCF-7) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mechanistically, the apoptotic effects on the Bax, Bcl2 and Caspase 3 were determined via quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Further, the antiviral activity was assessed against Adv-5 based on virucidal and adsorption mechanisms. RESULTS: The HPLC/MS analysis of the extract revealed tentative identification of twenty compounds of polyphenolic nature, mainly flavonoids, lignans, coumarins, and anthocyanidins. The plant extract showed a cytotoxic effect against MCF-7 and Vero cells with IC50 values of 15.50 and 44 µg/ml, respectively, indicating its aggressiveness against the proliferation of breast cancer cells as confirmed by apoptotic genes expression which revealed upregulation of Bax and Caspase 3 but further insight analysis is needed to explore exact mechanistic pathway. Antiviral activity against Adv-5 was observed at a non-toxic concentration of the tested extract. CONCLUSIONS: Such observations against human breast cancer and viral replication supported further studies for nanoformulations in drug delivery systems as targeting therapy and in vivo studies before biomedical applications.

Enhancement of Antioxidant Properties of the Medicinal Plant, Costus Pictus by Optimization of its Drying and Extraction Criteria.

Antioxidants act as major protective factors against different infections and diseases. The search for natural antioxidants has gained significant momentum due to its associated health benefits. It prompted the investigation of the antioxidant properties of widely recognized medicinal plants, considering their prominent role in conventional medicine. The incorporation of natural antioxidants derived from medicinal plants into food products has the potential to enhance their health benefits. The present investigation is the first study on the optimization of drying and extraction techniques in Costus pictus leaves. C. pictus leaves were dried under varying conditions (40, 50 and 60 °C) and dried powders were subjected to various solvents, namely water, ethanol, methanol and ethyl acetate. The leaves dried at 60 °C and treated with ethanol showed improved activities and were subsequently selected for further extraction. Among the various extraction methods, ultrasound-assisted extraction demonstrated superior antioxidant properties and increased phytochemical contents, making it the optimal technique for our study. Fourier transform infrared spectroscopy (FTIR) reports also substantiated these quantitative results. The extraction process played a significant role in enhancing the desirable attributes and properties of the leaf extracts, surpassing the results obtained from both dried and fresh leaves. The application of liquid chromatography-mass spectrometry (LC-MS) analysis to the leaf extracts facilitated the identification of phenolic compounds and flavonoids, presenting a comprehensive insight into the composition of the extract. Exploration of antioxidant properties, phenolic compounds and flavonoids would validate the benefits and expand the applications of C. pictus in functional foods and nutraceuticals.

The Aqueous Leaf Extract of the Medicinal Herb Costus speciosus Suppresses Influenza A H1N1 Viral Activity under In Vitro and In Vivo Conditions.

This study investigated the antiviral activity of aqueous leaf extract of Costus speciosus (TB100) against influenza A. Pretreatment of TB100 in RAW264.7 cells enhanced antiviral activity in an assay using the green fluorescence-expressing influenza A/Puerto Rico/8/1934 (H1N1) virus. The fifty percent effective concentration (EC50) and fifty percent cytotoxic concentration (CC50) were determined to be 15.19 ± 0.61 and 117.12 ± 18.31 µg/mL, respectively, for RAW264.7 cells. Based on fluorescent microscopy, green fluorescence protein (GFP) expression and viral copy number reduction confirmed that TB100 inhibited viral replication in murine RAW264.7 and human A549 and HEp2 cells. In vitro pretreatment with TB100 induced the phosphorylation of transcriptional activators TBK1, IRF3, STAT1, IKB-α, and p65 associated with interferon pathways, indicating the activation of antiviral defenses. The safety and protective efficacy of TB100 were assessed in BALB/c mice as an oral treatment and the results confirmed that it was safe and effective against influenza A/Puerto Rico/8/1934 (H1N1), A/Philippines/2/2008 (H3N2), and A/Chicken/Korea/116/2004 (H9N2). High-performance liquid chromatography of aqueous extracts led to the identification of cinnamic, caffeic, and chlorogenic acids as potential chemicals for antiviral responses. Further confirmatory studies using these acids revealed that each of them confers significant antiviral effects against influenza when used as pretreatment and enhances the antiviral response in a time-dependent manner. These findings suggest that TB100 has the potential to be developed into an antiviral agent that is effective against seasonal influenza.

Genome assemblies and comparison of two Neotropical spiral gingers: Costus pulverulentus and C. lasius.

The spiral gingers (Costus L.) are a pantropical genus of herbaceous perennial monocots; the Neotropical clade of Costus radiated rapidly in the past few million years into over 60 species. The Neotropical spiral gingers have a rich history of evolutionary and ecological research that can motivate and inform modern genetic investigations. Here, we present the first 2 chromosome-level genome assemblies in the genus, for C. pulverulentus and C. lasius, and briefly compare their synteny. We assembled the C. pulverulentus genome from a combination of short-read data, Chicago and Dovetail Hi-C chromatin-proximity sequencing, and alignment with a linkage map. We annotated the genome by mapping a C. pulverulentus transcriptome and querying mapped transcripts against a protein database. We assembled the C. lasius genome with Pacific Biosciences HiFi long reads and alignment to the C. pulverulentus genome. These 2 assemblies are the first published genomes for non-cultivated tropical plants. These genomes solidify the spiral gingers as a model system and will facilitate research on the poorly understood genetic basis of tropical plant diversification.

Dolomiaea costus: an untapped mine of sesquiterpene lactones with wide magnificent biological activities.

Dolomiaea costus (Falc.) Kasana & A.K. Pandey Family Asteraceae, formerly known as Saussurea costus (Falc.) Lipsch contains a rich treasury of diverse bioactive compounds such as monoterpenes, sesquiterpenes, triterpenes, sterols, cardenolides, flavonoids, coumarins, lignans, phenylpropanoids and alkaloids. The sesquiterpene lactones, costunolide and dehydrocostuslactone in D. costus, possess unique promising in vitro and in vivo biological activities for the prevention and cure of diverse ailments like Parkinson's disease, oxidative stress, hyperpigmentation, ulcerative colitis, breast cancer, hepatocellular carcinoma, colon cancer, prostate cancer, ovarian cancer, leukemia, stomach cancer, prostate cancer, lung cancer, osteosarcoma, neuroblastoma, allergy, type 2 diabetes, hepatotoxicity, bronchitis, pulmonary fibrosis, thrombosis and various microbial infections. Costunolide and dehydrocostuslactone are potential drug candidates that could lead to the development of new medications for a variety of difficult-to-treat diseases.

Evolutionary convergence on hummingbird pollination in Neotropical Costus provides insight into the causes of pollinator shifts.

The evolution of hummingbird pollination is common across angiosperms throughout the Americas, presenting an opportunity to examine convergence in both traits and environments to better understand how complex phenotypes arise. Here we examine independent shifts from bee to hummingbird pollination in the Neotropical spiral gingers (Costus) and address common explanations for the prevalence of transitions from bee to hummingbird pollination. We use floral traits of species with observed pollinators to predict pollinators of unobserved species and reconstruct ancestral pollination states on a well-resolved phylogeny. We examine whether independent transitions evolve towards the same phenotypic optimum and whether shifts to hummingbird pollination correlate with elevation or climate. Traits predicting hummingbird pollination include small flower size, brightly colored floral bracts and the absence of nectar guides. We find many shifts to hummingbird pollination and no reversals, a single shared phenotypic optimum across hummingbird flowers, and no association between pollination and elevation or climate. Evolutionary shifts to hummingbird pollination in Costus are highly convergent and directional, involve a surprising set of traits when compared with other plants with analogous transitions and refute the generality of several common explanations for the prevalence of transitions from bee to hummingbird pollination.

Green synthesis of Mn3O4 nanoparticles using Costus woodsonii flowers extract for effective removal of malachite green dye.

The pollution of organic dyes such as malachite green is one of the globally critical issues, calling for efficient mitigation methods. Herein, we developed green Mn3O4 nanoparticles synthesized using natural compounds extracted from Costus woodsonii flowers under an ultrasound-assisted mode. The materials were characterized using several physicochemical techniques such as Fourier-transform infrared spectroscopy, X-ray diffraction, Energy-dispersive X-ray spectroscopy, scanning electron microscopy, Raman spectroscopy, and N2 adsorption desorption isotherm measurement. The X-ray diffraction and N2 isotherm plots confirmed the presence of tetragonal γ-Mn3O4 phase and mesoporous structure, respectively. Carbonyl groups derived from flavonoids or carboxylic compounds were found in the surface of green Mn3O4 nanoparticles. The effect of pH, contact time, dose, and concentration on the adsorption of malachite green over green Mn3O4 was carried out. The maximum malachite green adsorption capacity for green Mn3O4 nanoparticles was 101-162 mg g-1. Moreover, kinetic and isotherm adsorption of malachite green obeyed Langmuir (Radj.2 = 0.980-0.995) and pseudo first-order models (Radj.2 = 0.996-1.00), respectively. Adsorption of malachite green over green Mn3O4 was a thermodynamically spontaneous process due to negative Gibbs free energy values (ΔGο < 0). Green Mn3O4 nanoparticles offered a high stability through the FR-IR spectra analysis. With a good recyclability of 4 cycles, green Mn3O4 nanoparticles can be used as potential adsorbent for removing malachite green dye from water.

Root extracts of Saussurea costus as prospective detoxifying food additive against sodium nitrite toxicity in male rats.

The goal of this study was to investigate the effects of three different extracts of Saussurea costus roots (ethanol, methanol, and water) as a food additive in alleviating the harmful effect of sodium nitrite in rat meals. Thirty-five adult male rats were divided into five groups as follows: control, sodium nitrite (NaNO2; 75 mg/kg BW, single oral dose), S. costus 70% ethanol, 70% methanol, and aqueous extracts (300 mg/kg BW), respectively for four weeks followed by a single dose of NaNO2 24h before decapitation. Results showed that the 70% ethanol extract of S. costus has a higher concentration of total phenolic content, total flavonoids, and antioxidant effect than the 70% methanol and water extracts. Rats pretreated with S. costus extracts reduced the harmful effects induced by NaNO2 and improved the hematological parameters, liver, and kidney function biomarkers as well as lipid profile as compared to the NaNO2 group. Furthermore, S. costus improved the histopathological alterations in the liver and kidney induced by NaNO2 and improved meat sensory evaluation. Conclusively, the 70% ethanol extract of S. costus roots is the most effective extract as an antioxidant against the toxicity of sodium nitrite in male rats and might be used safely as a natural additive in the food industry.

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.

Two new biologically active steroids from Costus lucanusianus (Costaceae).

A phytochemical investigation of the leaf extract of Costus lucanusianus J. Braun & K. Schum (Family Costaceae) a tropical African medicinal plant known for curing several infectious diseases such as venereal disease, cough and urinary tract infection led to the isolation of two new steroids. The identification of these isolates was achieved by modern spectroscopic methods, including 2D NMR. The in vitro antimicrobial activity and Minimum Inhibition Concentration (MIC) values of the isolated compounds against six bacterial and four fungi strains were evaluated. Compound Xp named 3,27-dihydroxy-1-methoxy-22-cholest-5-enone and compound 1 named ß-sitosterol-3-O-ß-D-3-deoxyxylo-4-hydroxy4,5-dimethyl-pent-2-one displayed broad antimicrobial activity at concentration 12.5 µg/mL-100 µg/mL. Compound Xp displayed MIC value 25.0 µg/mL against tested micro-organisms except for P. notatum and R. stolonifer which showed no prominent growth. Compound 1 was insufficient to determine the MIC value. This present study may be helpful in discovering new chemical groups of antimicrobial compounds that could be useful as an agent against infectious diseases.

Nephroprotective Effect of Costus (Saussurea costus) Ethanolic Extract on Oxaliplatin®-induced Nephrotoxicity in Adult Male Wistar Rats.

<b>Background and Objective:</b> Oxaliplatin^® is an antineoplastic platinum-based compound; nephrotoxicity is one of its most serious side effects. This study aimed to explore the nephroprotective potential of Costus Ethanolic Extract (CEE) against Oxaliplatin^®-induced nephrotoxicity. <b>Materials and Methods:</b> Adult male Wistar rats, weighting 140-160 g, were randomly divided into four groups: (1) Normal rats, (2) Rats ingested with CEE (67.08 mg kg¹ day¹), (3) Rats injected (ip) with Oxaliplatin^® (10 mg kg¹ week¹) and (4) rats treated with CEE in combination Oxaliplatin^® injection. <b>Results:</b> After six weeks of treatments, the results revealed that CEE ingestion along with Oxaliplatin^® injection markedly minimized the Oxaliplatin^®-induced renal deterioration; this was evidenced by the significant reduction in serum urea, creatinine, uric acid, Tumor Necrosis Factor Alpha (TNF-α), Interleukin 1Beta (IL¹ß) and Sodium ion (Na⁺) levels as well as kidney Malondialdehyde (MDA), Nitric Oxide (NO) and DNA fragmentation values. Controversially, a marked rise in serum Calcium, Potassium Ion (K⁺) and Cluster of Differentiation 4 (CD4) levels besides renal Glutathione (GSH), Catalase (CAT) and Superoxide Dismutase (SOD) values. Similarly, the histopathological findings confirmed the biochemical ones as the CEE restored the Oxaliplatin^®-induced histological degenerations. <b>Conclusion:</b> In conclusion, CEE exhibited nephron-protection efficiency against Oxaliplatin^®-induced nephrotoxicity; this promising effect may be achieved through the antioxidant and radical scavenging activities of its constituents.

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.