Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration.

Fumaria indica (Hausskn.) Pugsley (FIP), a member of the Papaveraceae family, has a documented history of use in traditional medicine to treat cardiovascular ailments, particularly hypertension, and has shown substantial therapeutic efficacy among native cultures worldwide. However, the identification of bioactive compounds and the mechanism of hypotensive effect with the cardioprotective potential investigations are yet to be determined. The study aimed to identify bioactive compounds, explore the hypotensive mechanism and cardioprotective potential, and assess the safety of Fumaria indica (Hausskn.) Pugsley hydromethanolic extract (Fip.Cr). LC ESI-MS/MS analysis was performed to identify the bioactive compounds. In vitro experiments were conducted on isolated rat aorta and atria, and an in vivo invasive BP measurement model was used. Acute and subacute toxicities were assessed for 14 and 28 days, respectively. Isoproterenol (ISO) was used to develop the rats' myocardial infarction damage model. The mRNA levels of NLRP3 inflammasome and the abundance level of Firmicutes and Lactobacillus were measured by qRT-PCR. The hypotensive effect of FIP bioactive compounds was also investigated using in silico methods. Fip. Cr LC ESI-MS/MS analysis discovered 33 bioactive compounds, including alkaloids and flavonoids. In isolated rat aorta, Fip.Cr reversed contractions induced by K+ (80 mM), demonstrating a calcium entry-blocking function, and had a vasorelaxant impact on phenylephrine (PE) (1 µM)-induced contractions unaffected by L-NAME, ruling out endothelial NO participation. Fip.Cr caused negative chronotropic and inotropic effects in isolated rat atria unaffected by atropine pretreatment, eliminating cardiac muscarinic receptor involvement. Safety evaluation showed no major adverse effects. In vivo, invasive BP measurement demonstrated a hypotensive effect comparable to verapamil. Fip.Cr protected the rats from ISO-induced MI interventions significantly in biometrical and cardiac serum biochemical indicators and histological examinations by reducing inflammation via inhibiting NLRP3 inflammasome and elevating Firmicutes and Lactobacillus levels. The network pharmacology study revealed that the FIP hypotensive mechanism might involve MMP9, JAK2, HMOX1, NOS2, NOS3, TEK, SERPINE1, CCL2, and VEGFA. The molecular docking study revealed that FIP bioactive compounds docked better with CAC1C_ HUMAN than verapamil. These findings demonstrated that Fip.Cr's hypotensive mechanism may include calcium channel blocker activity. Fip.Cr ameliorated ISO-induced myocardial infarction in rats by attenuating inflammation, which might be via inhibiting NLRP3 inflammasome and may prove beneficial for treating MI.

Green Synthesis and Evaluation of Lepidium didymum-mediated Silver Nanoparticles for in vitro Antibacterial Activity and Wound Healing in the Animal Model.

Wounds serve as an appropriate medium for the growth of pathogenic bacteria, and bacterial resistance to already available antibiotics demands new and safe approaches in the field of medicine. Silver nanoparticles (AgNPs) exhibited a wide range of applications in biomedicine and emerged as promising nano-antibiotics. The biological preparation of AgNPs by utilizing aqueous plant extract has become an encouraging alternative to traditional chemical methodologies, owing to a viable eco-friendly approach. In the present study, Lepidium didymum leaves extract was used for the biosynthesis of AgNPs-LD. The nanoparticles were characterized through UV-Vis spectroscopy, Fourier transforms infrared spectrometry (FTIR), Scanning electron microscopy (SEM), and X-ray diffraction (XRD). The antibacterial activity of AgNPs-LD was evaluated against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Further, AgNPs-LD nanoparticles were incorporated into topical gels to evaluate their effectiveness for wound healing in the rat model. UV-visible spectra showed a surface resonance peak around 400 nm correlated with the synthesis of AgNPs; FTIR spectra verified the participation of phytochemicals present in L. didymum leaves extract in AgNPs-LD synthesis; and SEM revealed dispersed spherical nanoparticles as well as aggregated clusters. XRD analysis confirmed the crystalline nature, face-centered cubic lattice, and average crystallite size of 21.42 nm. The AgNPs-LD showed promising antibacterial activity against tested strains with a maximum zone of inhibition against P. aeruginosa and showed accelerated wound healing capacity comparable to control and standard treatments over the time course of wound healing. The current study concluded that biosynthesized AgNPs-LD nanoparticles are effective as antibacterial agents and are promising novel wound healing products for clinical applications.

Investigations of plausible pharmacodynamics supporting the antispasmodic, bronchodilator, and antidiarrheal activities of Berberis lycium Royle. Via in silico, in vitro, and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberis lycium Royle, a member of the Berberidaceae family, is a high-value medicinal plant with a documented history of usage in traditional medicine and has demonstrated significant therapeutic results among local populations throughout the globe. It is used traditionally in many parts of Pakistan to treat diarrhea, abdominal spasms, coughs, and chest problems. AIM OF THE STUDY: To investigate the antispasmodic, bronchodilator, and antidiarrheal effects of B. lycium and its possible underlying mechanisms through in silico, in vitro, and in vivo studies. MATERIALS AND METHODS: LC ESI-MS/MS analysis was used to identify bioactive components within the hydromethanolic extract of B. lycium. In silico studies, including network pharmacology and molecular docking, were utilized to investigate the antispasmodic and bronchodilator properties of the extract's bioactive components. In vitro pharmacological studies were conducted using isolated rabbit jejunum, trachea, urinary bladder, and rat ileum preparations. In vivo antidiarrheal activities were conducted in mice, including castor oil-induced diarrhea, intestinal transit, and castor oil-induced enteropooling. RESULTS: The LC ESI-MS/MS analysis of the hydromethanolic extract of B. lycium identified 38 bioactive compounds. Network pharmacology study demonstrated that the mechanism of BLR for the treatment of diarrhea might involve IL1B, TLR4, PIK3R1, TNF, PTPRC, IL2, PIK3CD, and ABCB1, whereas, for respiratory ailments, it may involve PIK3CG, TRPV1, STAT3, ICAM1, ACE, PTGER2, PTGS2, TNF, MMP9, NOS2, IL2, CCR5, HRH1, and VDR. Molecular docking research revealed that chlorogenic acid, epigallocatechin, isorhamnetin, quinic acid, gallic acid, camptothecin, formononetin-7-O-glucoside, velutin, caffeic acid, and (S)-luteanine exhibited a higher docking score than dicyclomine with validated proteins of smooth muscle contractions such as CACB2_HUMAN, ACM3_HUMAN, MYLK_HUMAN, and PLCG1_HUMAN. In vitro investigations demonstrated that Blr.Cr, Blr.EtOAc, and Blr.Aq relaxed spontaneously contracting jejunum preparations; carbachol (1 µM)-induced and K+ (80 mM)-induced jejunum, trachea, and urinary bladder contractions in a concentration-dependent manner, similar to dicyclomine. Moreover, Blr.Cr, Blr.EtOAc, and Blr.Aq exhibited a rightward shift in Ca+2 and carbachol cumulative response curves, similar to dicyclomine, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanisms due to the presence of alkaloids and flavonoids. In vivo antidiarrheal activities showed that the hydromethanolic extract was significantly effective against castor oil-induced diarrhea and castor oil-induced enteropooling, similar to loperamide, and charcoal meal intestinal transit, similar to atropine, in mice at doses of 50, 100, and 200 mg/kg body weight, which supports its traditional use in diarrhea. CONCLUSION: The dual blocking mechanism of muscarinic receptors and Ca+2 channels behind the smooth muscle relaxing activity reveals the therapeutic relevance of B. lycium in diarrhea, abdominal spasms, coughs, and chest problems.

Hepatoprotective effect of methanolic extract of Iris florentina L. on paracetamol-induced liver toxicity in rats.

Despite of plethora of research on hepatoprotective potential of medicinal plants, there is still need to discover potential plants with hepatoprotective activity. Iris florentina L. is a medicinal plant with traditional claims but ignored investigation regarding its hepatoprotective effects. The current study is aimed to investigate the hepatoprotective potential of I. florentina L. methanolic extract on paracetamol (PCM)-induced liver injury. The phytochemical and HPLC screening was done which showed the presence of potential constituents including flavonoids and phenols. For investigating the hepatoprotective effect of I. florentina L. methanolic extract, rats were given five different treatments for seven consecutive days. The normal control (group 1) was administered with normal saline, group 2 (Diseased) received paracetamol and group 3 (Standard) was given silymarin as reference drug. In group 4 and 5 (Treated), I. florentina L. methanolic extract (250 and 500mg/kg) were administered. Different serum biomarkers and histopathological studies were performed to assess the recovery caused by PCM in comparison to diseased group. The treatment of I. florentina methanolic extract significantly improve the serum biomarkers and restored the hepatic injury towards normal, indicating the hepatoprotective potential. Thus, we can conclude that I. florentina have significantly reversed the damage caused by paracetamol in hepatotoxic rat model due to their potential phytochemical constituents.

Chronically administered Agave americana var. marginata extract ameliorates diabetes mellitus, associated behavioral comorbidities and biochemical parameters in alloxan-induced diabetic rats.

Introduction: Diabetes mellitus causes hyperglycemia and associated complications to the brain. In current study, the traditionally reported remedial claims of Agave americana var. marginata has been scientifically investigated in diabetic rats. Methodology: The methanolic extract of leaves of Agave americana var. marginata (Aa.Cr) was characterized for total phenols, flavonoids, and antioxidant potential through in-vitro testing. The rats chronically pre-treated with Aa.Cr (400 and 600 mg/kg) for 45 days were challenged with alloxan-induced hyperglycemia. The dose-dependent effects of Aa.Cr on blood glucose levels and body weights were compared with diabetic rats using glibenclamide (0.6 mg/kg) as a standard. The animals were tested for diabetes-associated neurological comorbidities through behavioral and biochemical evaluation. Results: The phenols and flavonoids enriched Aa.Cr caused a significant dose-dependent hypoglycemic effect. Aa.Cr showed protection from comorbid anxiety, depression and cognitive impairment as compared to diabetic rats. The alanine aminotransferase, total cholesterol, triglycerides and low-density lipoprotein were prominently reduced, and high-density lipoprotein was increased in rats treated with Aa.Cr. Moreover, the oxidative stress in isolated brains was reduced by Aa.Cr. Conclusion: These findings suggest that Aa.Cr is enriched with antioxidant and anti-inflammatory phytoconstituents valuable for diabetes and related neurological complications.

Analgesic and Anti-Inflammatory Properties of Two Hydrogel Formulations Comprising Polyherbal Extract.

Background: Nature represents a basic source of medicinal scaffolds that can develop into potent drugs used in the treatment of many diseases. Aim: The present study was planned to evaluate the combined effects of polyherbal methanolic extract of the herbs (fruit of capsicum, bark of cinnamon, rhizome of turmeric and rhizome of ginger) that were individually well known for their analgesic and anti-inflammatory activities. Furthermore, we aimed to develop hydrogel formulation of this polyherbal extract and to characterize and evaluate its analgesic and anti-inflammatory potential. Materials and Methods: Zingiber officinale (R.), Capsicum annuum (L.), Curcuma longa (L.), and Cinnamomum verum (J.) polyherbal extract (GCTC) was prepared by maceration and evaluated for analgesic and anti-inflammatory potential. Then, two different types of hydrogel formulation were prepared. One is pH-based hydrogel in which carbopol-940 was used and the other is temperature-based gel in which methocel-K100 was used as gelling agent. Different concentrations of polyherbal extract (GCTC), at 1%, 3% and 5%, were used in hydrogel formulation. These prepared hydrogel formulations were characterized and evaluated for analgesic and anti-inflammatory potential. Results: Results show that polyherbal extract and all the developed formulations of polyherbal extract (GCTC), at concentrations of 1%, 3% and 5%, have significant analgesic and anti-inflammatory effects with good appearance, homogeneity, spreadability, extrudability and stability. Conclusion: It was concluded from this project that polyherbal extract (GCTC) and its hydrogel have significant analgesic and anti-inflammatory potential.

Design and Characterization of Agarose/HPMC Buccal Films Bearing Ondansetron HCl In Vitro and In Vivo: Enhancement Using Iontophoretic and Chemical Approaches.

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 µg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 µg/min, 399.35 µg/min, and 244.81 µg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.

Hyperglycemia-associated Alzheimer's-like symptoms and other behavioral effects attenuated by Plumeria obtusa L. Extract in alloxan-induced diabetic rats.

Diabetes mellitus is a chronic metabolic complaint with numerous short- and long-term complications that harm a person's physical and psychological health. Plumeria obtusa L. is a traditional medicine used in the treatment of diabetes to reduce complications related to behavior. Plumeria is a genus with antipsychotic activities. The objective of this study was to examine the effects of a methanolic extract of Plumeria obtusa L. in the attenuation of diabetes, on symptoms of Alzheimer disease, and on other associated behavioral aspects. A single dose of alloxan was administered to an experimental group of rats to induce development of diabetes (150 mg/kg, intraperitoneal) and the rats were then administered selected doses of methanolic extract of Plumeria obtusa L. (Po.Cr) or glibenclamide (0.6 mg/kg) for 45 consecutive days. Behavioral effects were evaluated using three validated assays of anxiety-related behavior: the open field test, the light and dark test, and the elevated plus maze. Anti-depressant effects of Plumeria obtusa L. were evaluated using the forced swim test (FST) and memory and learning were assessed using the Morris water maze (MWM) task. Po.Cr was also evaluated for phytochemicals using total phenolic content (TPC), total flavonoid content (TFC), and high-performance liquid chromatography assays, and antioxidant capability was assessed through assays of DPPH radical scavenging, total oxidation capacity, and total reducing capacity. In the alloxan-induced model of diabetes, the administration of Po.Cr and glibenclamide for 45 days produced a marked decrease (p < 0.001) in hyperglycemia compared to control animals. Po.Cr treatment also resulted in improvement in indicators, such as body weight and lipid profile (p < 0.05), as well as restoration of normal levels of alanine transaminase (ALT) (p < 0.001), a biomarker of liver function. Diabetic rats presented more Alzheimer-like symptoms, with greater impairment of memory and learning, and increased anxiety and depression compared to non-diabetic normal rats, whereas treated diabetic rats showed significant improvements in memory and behavioral outcomes. These results demonstrate that Po.Cr reversed alloxan-induced hyperglycemia and ameliorated Alzheimer-related behavioral changes, which supports additional study and assessment of conventional use of the plant to treat diabetes and associated behavioral complications.

Formulation and characterization of lornoxicam-loaded cellulosic-microsponge gel for possible applications in arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease associated with severe joint pain. Herein, we report lornoxicam loaded cellulosic microsponge gel formulation with sustained anti-inflammatory effects that are required to manage arthritic pain. The microsponges were formulated using quasi emulsion-solvent diffusion method employing four different surfactant systems, namely polyvinyl alcohol (PVA), Tween80, Gelucire 48/16 and Gelucire 50/13. All the lornoxicam loaded microsponge formulations were extensively characterized with a variety of analytical tools. The optimized microsponge formulation was then converted into gel formulation. The lornoxicam loaded microsponge gel formulation had adequate viscosity and sufficient pharmaceutical properties as confirmed by the texture analysis and the drug release followed Super case II transport. It is noteworthy that we described the preparation of a new cellulosic polymers based microsponge system for delivery of lornoxicam to provide quick as well as lasting (sustained) anti-inflammatory effects in rats using carrageenan induced rat paw edema model. We were able to demonstrate a 72% reduction in inflammation within 4 h using the optimize transdermal gel formulation utilizing Transcutol P as permeation enhancer and with the aid of skin micro-piercing by microneedles, hence, demonstrating the potential of this microsponge gel formulation in arthritis management.

Pharmacological exploration of traditional plants for the treatment of neurodegenerative disorders.

Alzheimer's disease (AD) is clinically characterized as memory deficits, altered behavior and impaired cognitive functions. The most important risk factor for AD is aging and mounting. Evidences suggested in different studies that traditionally used plants in Asia, China, and Europe significantly affect aging and AD involved neurodegeneration pathways. Research into ethnobotanicals for impaired memory and cognition has been burgeoned in last decades. The inclusion and exclusion criteria for the plant selection were based on reputed herbs recommended for treatment of neurological disorders and their scientific validation to cure neurodegenerative disorders. A range of traditional plants imparts effects via acetylcholinesterase activity, ß-amyloid peptide formation in plaques, neurotrophic factors and through antioxidant activity. On one side preclinical investigations identified promising drug candidates for AD, on the other side, clinical evidences are still pending. Presently, according to WHO, around more than 80% world population relay on natural remedies to cure their health related issues. Plants contain rich source of primary and secondary metabolites for improving health problems. Pharmaceutical industry is facing intriguing challenges like elevated cost and unendurable risk management due to the high burden of neurodegenerative disorders. A significant shift of drug discovery is being witnessed from synthetic moieties to herbal formulation.

Antiplatelet Aggregation, Cardiotonic, Anti-Inflammatory, Antioxidant, and Calcium Channel Antagonistic Potentials of Nepeta ruderalis Buch.

The objective of this study was to authenticate the ethnobotanical claims of the Nepeta ruderalis Buch.-Ham. (N. ruderalis) extract in the traditional system of medicine. Crude extract was prepared via a simple maceration process. DPPH free radical scavenging and carrageenan-induced rat paw edema models were used to monitor antioxidant and anti-inflammatory responses of the N. ruderalis extract. Furthermore, it was tested for antiplatelet aggregation, cardioprotective, and calcium channel antagonistic activities via standard documented protocols. The N. ruderalis extract exhibited 80.82% antioxidant activity (IC50 = 207.51 ± 4.36 µg) while the anti-inflammatory response was significant (p < 0.05 to p < 0.01) at 50 mg/kg (45.58%) and 100 mg/kg (60.90%) doses. Moreover, it was found to inhibit platelet aggregation (IC50 = 1.06 and 0.91 mg/mL) and, in addition, to increase the force of contraction at the concentration of 3.0-10 mg/mL with a decrease in the heart rate on isolated paired atria (EC50 = 11.78 mg/mL). Relaxant activity was observed on the isolated rabbit jejunum (EC50 = 0.96 mg/mL) and trachea (EC50 = 0.89 mg/mL). However, in a cumulative way, an 80-millimolar potassium-induced contraction was evaluated (EC50 = 1.31 mg/mL). The N. ruderalis extract exhibited antioxidant, anti-inflammatory, platelet aggregating, cardiotonic, and calcium channel antagonistic activities, therefore proving scientifically its effectiveness in the traditional system of medicine.

The Potential Involvement of an ATP-Dependent Potassium Channel-Opening Mechanism in the Smooth Muscle Relaxant Properties of Tamarix dioica Roxb.

Background: Tamarix dioica is traditionally used to manage various disorders related to smooth muscle in the gastrointestinal, respiratory, and cardiovascular systems. This study was planned to establish a pharmacological basis for the uses of Tamarix dioica in certain medical conditions related to the digestive, respiratory, and cardiovascular systems, and to explore the underlying mechanisms. Methods: A phytochemical study was performed by preliminary methods, followed by HPLC-DAD and spectrometric methods. In vivo evaluation of a crude hydromethanolic extract of T.dioica (TdCr) was done with a castor-oil-provoked diarrheal model in rats to determine its antidiarrheal effect. Ex vivo experiments were done by using isolated tissues to determine the effects on smooth and cardiac muscles and explore the possible mechanisms. Results: TdCr tested positive for flavonoids, saponins, phenols, and tannins as methanolic solvable constituents in a preliminary study. The maximum quantity of gallic acid equivalent (GAE), phenolic, and quercetin equivalent (QE) flavonoid content found was 146 ± 0.001 µg GAE/mg extract and 36.17 ± 2.35 µg QE/mg extract. Quantification based on HPLC-DAD (reverse phase) exposed the presence of rutin at the highest concentration, followed by catechin, gallic acid, myricetin, kaempferol, and apigenin in TdCr. In vivo experiments showed the significant antidiarrheal effect of TdCr (100, 200, and 400 mg/kg) in the diarrheal (castor-oil-provoked) model. Ex vivo experiments revealed spasmolytic, bronchodilatory, and vasorelaxant activities as well as partial cardiac depressant activity, which may be potentiated by a potassium channel opener mechanism, similar to that of cromakalim. The potassium channel (KATP channel)-opening activity was further confirmed by repeating the experiments in glibenclamide-pretreated tissues. Conclusions: In vivo and ex vivo studies of T.dioica provided evidence of the antidiarrheal, spasmolytic, bronchodilator, vasorelaxant, and partial cardiodepressant properties facilitated through the opening of the KATP channel.

Dual mechanisms of anti-muscarinic and Ca++ antagonistic activities to validate the folkloric uses of Cyperus niveus Retz. as antispasmodic and antidiarrheal.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus species are famous for their traditional uses and very commonly used for their anti-spasmodic and anti-diarrheal activities. Cyperus niveus Retz. is used in local traditional system of medicine in Pakistan to treat diarrhea and emesis. AIM OF THE STUDY: The aim of the study was to validate the traditional uses and to provide the possible mechanisms for the medicinal use of Cyperus niveus Retz. as anti-spasmodic, anti-diarrheal and anti emetic. MATERIALS AND METHODS: The in-vivo studies of anti-diarrheal, charcoal meal GI transit test and anti-emetic activities were conducted in rats, mice and chicks respectively, while isolated tissues of rabbit's jejunum and rat's ileum were used for in-vitro experiments. Phytochemical analysis was also undertaken. RESULTS: The phytochemical study of hydro-ethanolic extract of Cyperus niveus Retz. showed the presence of flavonoids, phenols, alkaloids, tannins, saponins and glycosides. Cn. Cr caused significant inhibition of castor oil-induced diarrhea in rats (300,500 & 700mg/kg) using loperamide (10mg/kg, p.o) as standard. Cn. Cr also significantly decreased the motility in charcoal meal GI transit test at 100-200mg/kg in mice, using atropine (3.0mg/kg) as positive control. In jejunum tissue, Cn. Cr relaxed carbachol(1µM) and K+(80mM)-induced contractions, similar to the effect of dicyclomine. Pre-incubation of isolated rat ileum tissues with Cn. Cr (0.1mg/mL) caused the corresponding shift of CCh concentration response curve (CRC) to right without decrease in max. response whereas at the concentration of 0.3mg/mL caused the rightward nonparallel shift with max. response suppression, similar to dicyclomine. Antimuscarinic effect was further confirmed when prior administration of Cn. Cr (0.1, 0.3 and 1mg/mL) caused concentration dependent inhibition of induced contractions of carbachol, comparable to atropine (1µM). To confirm the Ca2+ channel blocking (CCB), the rabbit jejunum was pre-incubated with Cn. Cr (0.3 & 1.0mg/mL), produced a shift in CRCs of calcium toward right with decrease in the maximum response at next concentration, similar to that of dicyclomine. The organic fraction of Cyperus niveus Retz. (Cn. Dcm) showed Ca2+ antagonist and anticholinergic activities with higher potency against K+(80mM) induced contractions, like verapamil, while aqueous fraction (Cn. Aq) relaxed only carbachol(1µM) induced contractions with no prominent effect on K+ (80mM)-contractions even at the higher concentration of 10mg/mL, similar to atropine. Cn. Cr also showed significant anti-emetic effect in Chick emesis model using chlorpromazine as standard. CONCLUSION: This study shows the presence of antidiarrheal and spasmolytic activities in Cyperus niveus Retz. extract, mediated by dual blocking mechanisms of muscarinic receptors and Ca2+ channels. The results further indicate the presence of anti-emetic activity in Cn. Cr, which may be because of its anti-muscarinic potential. This study provides the scientific bases to the traditional use of Cn. Cr in diarrhea and emesis.