Quality-by-design-based microemulsion of disulfiram for repurposing in melanoma and breast cancer therapy.

Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy. Materials & methods: The ME was formulated using Cinnamon oil & Tween® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Zavg) and polydispersity index (PDI). Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF. Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.

Identifying new medicinal uses of an existing marketed drug can save both money and time in the process of drug development. From many of the recently reported literature, disulfiram (a drug used for alcoholism) has shown its activity against various cancers, including breast and skin cancer. However, it possesses poor water solubility and absorption, leading to low medicinal activity. The current study aims to develop a novel microemulsion dosage form through a statistical design approach to enhance the solubility, dissolution and anticancer activity for repurposing in melanoma and breast cancer treatment. The novel microemulsion was prepared, statistically analyzed and optimized. The optimized microemulsion was found to be stable and showed improved medicinal activity against breast and skin cancer compared with the pure drug. Our research showed the potential of the developed microemulsion of the disulfiram for its new therapeutic use in skin cancer and breast cancer.

Harnessing exosomes and plant-derived exosomes as nanocarriers for the efficient delivery of plant bioactives.

Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150 nm, produced by various organisms through the endosomal pathway. Recent studies have established the utilization of exosomes as nanocarriers for drug distribution across various therapeutic areas including cancer, acute liver injury, neuroprotection, oxidative stress, inflammation, etc. The importance of plant-derived exosomes and exosome vesicles derived from mammalian cells or milk, loaded with potent plant bioactives for various therapeutic indications are discussed along with insights into future perspectives. Moreover, this review provides a detailed understanding of exosome biogenesis, their composition, classification, stability of different types of exosomes, and different routes of administration along with the standard techniques used for isolating, purifying, and characterizing exosomes.

Exosomes are tiny, spherical structures made of two layers of lipids, measuring between 30 and 150 nm in diameter. They are flexible, less harmful to the immune system, can cross barriers in the body, and also can be used as vehicles to carry drugs. Various methods are used to obtain, separate, and purify the exosomes based on their size, shape, density, and specific markers. Exosomes obtained from plants can treat various diseases as they are less toxic, have high permeability, and are environmentally safe. The chemical compounds obtained from plants can be loaded into the exosomes obtained from sources like milk, or human cells both healthy and diseased, having the ability to treat cancer, inflammation, liver diseases, etc.

Nanovesicular ultraflexible invasomes and invasomal gel for transdermal delivery of phytopharmaceuticals.

Tweetable abstract Invasomes and invasomal gel are ultraflexible, soft vesicular, phospholipid based nanocarriers with deeper skin penetration ability for transdermal applications of drugs and phytopharmaceuticals.

Quality-by-design-based development of ultradeformable nanovesicular transgelosome of standardized Piper longum extract for melanoma.

Background: Melanoma is the most aggressive and deadly form of skin cancer. The stratum corneum of the skin is a major obstacle to dermal and transdermal drug delivery. Ultradeformable nanovesicular transferosome has the capacity for deeper skin penetration and its incorporation into hydrogel forms a transgelosome that has better skin permeability and patient compliance. Method: Here, the quality-by-design-based development and optimization of nanovesicular transgelosome of standardized Piper longum fruit ethanolic extract (PLFEE) for melanoma therapy are reported. Results: Compared with standardized PLFEE-loaded plain gel, the transgelosome displayed optimal pharmaceutical properties and improved ex vivo skin permeability and in vivo tumor regression in B16F10 melanoma-bearing C57BL/6 mice. Conclusion: The results reflect the potential of transgelosome for melanoma therapy.

Melanoma is a deadly form of skin cancer that originates from melanocytes in the skin. Skin is a major barrier to drug delivery. Transferosome is a liquid nanoformulation that has the capacity for deeper skin penetration. The transferosome was prepared from standardized Piper longum fruit ethanolic extract (PLFEE) and loaded into gel to form a transgelosome for improved skin application and patient compliance. Compared with extract-loaded plain gel, the transgelosome showed good pharmaceutical properties with better activity in melanoma (B16F10)-bearing female C57BL/6 mice. The therapeutic activity of the standard anticancer drug dacarbazine was improved with the prepared PLFEE transgelosome.

Quality by design-based development and optimization of fourth-generation ternary solid dispersion of standardized Piper longum extract for melanoma therapy.

The study aimed to enhance the solubility, dissolution, and oral bioavailability of standardized Piper longum fruits ethanolic extract (PLFEE) via fourth-generation ternary solid dispersion (SD) for melanoma therapy. With the use of solvent evaporation method, the standardized PLFEE was formulated into SD, optimized using Box-Wilson's central composite design (CCD), and evaluated for pharmaceutical performance and in vivo anticancer activity against melanoma (B16F10)-bearing C57BL/6 mice. The optimized SD showed good accelerated stability, high yield, drug content, and content uniformity for bioactive marker piperine (PIP). The X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarized light microscopy (PLM), and selected area electron diffraction (SAED) analysis revealed its amorphous nature. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and high-performance thin layer chromatography (HPTLC) revealed the compatibility of excipients with the PLFEE. The contact angle measurement and in vitro dissolution study revealed excellent wetting of SD and improved dissolution profile as compared to the plain PLFEE. The in vivo oral bioavailability of SD reflected a significant (p < 0.05) improvement in bioavailability (Frel = 188.765%) as compared to plain extract. The in vivo tumor regression study revealed the improved therapeutic activity of SD as compared to plain PLFEE. Further, the SD also improved the anticancer activity of dacarbazine (DTIC) as an adjuvant therapy. The overall result revealed the potential of developed SD for melanoma therapy either alone or as an adjuvant therapy with DTIC.

Bioengineered dual fluorescent carbon nano dots from Indian long pepper leaves for multifaceted environmental and health utilities.

In this article, we present the synthesis of Piper longum leaves-derived ethanolic carbon dots (PLECDs) using the most simplistic environmentally friendly solvothermal carbonization method. The PLECDs fluoresced pink color with maximum emission at 670 nm at 397 nm excitation. Additionally, the dried PLECDs dissolved in water showed green fluorescence with higher emission at 452 nm at 370 nm excitation. The UV spectra showed peaks in the UV region (271.25 nm and 320.79 nm) and a noticeable tail in the visible region, signifying the efficient synthesis of nano-sized carbon particles and the Mie scattering effect. Various functional groups (-OH, -N-H, -C-H, -C = C, -C-N, and -C-O) were identified using Fourier transform infrared spectroscopy (FTIR). Its nanocrystalline property was revealed by the sharp peaks in the X-ray diffraction (XRD). High-resolution transmission electron microscopy (HRTEM) photomicrograph displayed a roughly spherical structure with a mean size of 2.835 nm. The energy dispersive X-ray (EDAX) and X-ray photoelectron spectroscopy (XPS) revealed the elemental abundance of C, O, and N. The high-performance thin-layer chromatography (HPTLC) fingerprint of PLECDs showed an altered pattern than its precursor (Piper longum leaves ethanolic extract or PLLEE). The PLECDs sensed Cu2+ selectively with a limit of detection (LOD) and limit of quantification (LOQ) of 0.063 µM and 0.193 µM, respectively. It showed excellent cytotoxicity toward MDA-MB-231 (human breast cancer), SiHa (human cervical carcinoma), and B16F10 (murine melanoma) cell lines with excellent in vitro bioimaging outcomes. It also has free radical scavenging activity. The PLECDs also showed outstanding bacterial biocompatibility, pH-dependent fluorescence stability, photostability, physicochemical stability, and thermal stability.

Chemometric-Based Analysis of Metabolomics Studies of Bioactive Fractions of Pleurotus osteratus and Their Correlation with In Vitro Anti-Cancer Activity.

Richness in nutrients with an ample of the myco-bioactive molecules makes Pleurotus osteratus preferential mushroom. In this paper, we conducted a preliminary study on bio-assay-guided fractionation of dichloromethane:ethanol crude extract (1:1, v/v) of P. osteratus (CD) against human breast cancer cell line (MDA-MB-231). Later, CD and its potent hexane (H) and ethyl acetate (EA) fraction were screened against a panel of a human cancer cell lines. H fraction possesses higher cytotoxicity followed by EA and CD. Literature review revealed that polyphenol and ergosterol are the biomarkers found in P. osteratus and could responsible for its cytotoxic potential. Accordingly, hyphenated liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based polyphenol and ergosterol-targeted myco-metabolite profiling of CD, H, and EA fractions were carried out. Despite being significantly rich in polyphenol and ergosterol content, EA fraction showed moderate cytotoxicity. Considering this, liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF/MS)-based untargeted myco-metabolite profiling of CD, H and EA fractions was further conducted to identify a new biomarker. Tentatively, 20 myco-metabolites were identified, belonging to the class of steroids, alkaloid, terpenoid, fatty alcohol, and polyketide. The myco-metabolite variabilities among potent samples in correlation to their in vitro anti-cancer activity was explored using the different chemometric tools: principal component analysis (PCA), hierarchical clustering analysis (HCA), and partial least square (PLS). A probable synergistic action among identified myco-metabolites (betulin, solanocapsine, ophiobolin F, linoleoyl ethanolamide, (13R,14R)-7-labdene-13,14,15-triol, asterosterol, cholest-5-ene, (3b,6b,8a,12a)-8,12-epoxy-7(11)-eremophilene-6,8,12-trimethoxy-3-ol, beta-obscurine, myxalamid B, momordol, and avocadyne 4-acetate) may be responsible for the observed cytotoxicity potential of H fraction of P. osteratus.

Tracing the Anti-cancer Mechanism of Pleurotus osteratus by the Integrative Approach of Network Pharmacology and Experimental Studies.

The present study identified the probable mechanism behind the anti-cancer activity of the hexane fraction of Pleurotus osteratus (HFPO) using network pharmacology and experimental validation. HFPO myco-metabolites targets and targets related to the cancer were mined from the online web server, and overlapping targets were screened. Out of the 74 overlapping targets, 33 targets were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of cancer. Furthermore, the main active myco-metabolites and hub targets were identified by network analysis of the compound-targets network and protein-protein interaction (PPI), respectively. Molecular docking results showed good binding affinity of the hub targets with their respective myco-metabolites. HFPO induced in-vitro anti-cancer activity by affecting the PI3K-AKT-mTOR pathway, besides time-dependent cell cytotoxicity and apoptotic cell body formation. Additionally, tumor volume reduction was observed in HFPO-treated Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. Overall, HFPO induces anti-cancer potential by modulating the PI3K-AKT-mTOR signaling pathway.

Tinospora cordifolia Leaves Derived Carbon dots for Cancer Cell Bioimaging, Free radical Scavenging, and Fe3+ Sensing Applications.

Herein, we report the fabrication of Tinospora cordifolia leaves-derived carbon dots (TCLCDs) from aqueous extract of leaves as carbon source via simple, environmentally friendly, hydrothermal carbonization (HTC) technique. The synthesized TCLCDs were characterized for their physicochemical properties and further explored for in-vitro cancer cell bioimaging, radical scavenging, and metal ion sensing. The synthesized TCLCDs showed excitation-dependent emission property with maximum emission at 435 nm under the excitation of 350 nm. The High-Resolution Transmission Electron Microscopy (HRTEM) results revealed a roughly spherical shape with an average diameter of 5.47 nm. The diffused ring pattern of Selected Area Electron Diffraction (SAED) and halo diffraction pattern of X-ray diffraction (XRD) disclosed their amorphous nature. The Energy Dispersive X-ray (EDX) showed the existence of C, N, and O. The Fourier-transform infrared spectroscopy (FTIR) revealed the presence of -OH, -NH, -CN, and -CH groups. The TCLCDs showed excellent cellular biocompatibility with dose-dependent bioimaging results in melanoma (B16F10) and cervical cancer (SiHa) cell lines. Also, they exhibited excellent scavenging of free radicals with an IC50 value of 0.524 mg/mL & selective Fe3+ ion sensing with a detection limit of 0.414 µM. Further, they exerted excellent bacterial biocompatibility, photostability, and thermal stability. The overall results reflected their potential for in-vitro cancer cell bioimaging, free radical scavenging, and selective Fe3+ ion sensing.

Natural Products and some Semi-synthetic Analogues as Potential TRPV1 Ligands for Attenuating Neuropathic Pain.

Natural products and leads inspired by them have acted as a probe for successful drug discovery for many decades. Pain is an obnoxious sensory and emotional experience associated with potential tissue damage. It affects the quality of life of patients to a greater extent. Despite the availability of several agents targeting TRP receptors, none of them can proficiently alleviate neuropathic pain. TRPV1 is a prospective target for treating neuropathic pain as it is recognized to modulate the pain circuitry at the periphery and the central level. In this review, we have discussed several natural molecules, such as Capsaicinoids, Capsinoids, Piperine, Eugenol, Scutigeral, Ginsenosides, Cinnamaldehyde, Camphor, Shogaol, Gingerols, Zingerone, Allicin, Evodiamine, Allylisothiocyanate, Cannabidiol, Ricinoleic acid, Isovelleral, Capsazepine, Thapsigargin, Pellitorine, Yohimbine, Curcumin and some semi-synthetic analogues that activate TRPV1 channels and consequently, can be further harnessed for the treatment of neuropathic pain.

Carbon dots from an immunomodulatory plant for cancer cell imaging, free radical scavenging and metal sensing applications.

Aim: This work aimed to develop Tinospora cordifolia stem-derived carbon dots (TCSCD) for cancer cell imaging, free radical scavenging and metal sensing applications. Method: The TCSCDs were synthesized by a simple, one-step, and ecofriendly hydrothermal carbonization method and characterized for their optical properties, morphology, hydrodynamic size, surface functionality, crystallinity, stability, bacterial biocompatibility, in vitro cellular imaging, free radical scavenging and metal sensing ability. Results: The TCSCDs exhibited excellent biocompatibility with dose-dependent bioimaging results in melanoma (B16F10) and cervical cancer (SiHa) cell lines. They exerted good free radical scavenging, Fe3+ sensing, bacterial biocompatibility, photostability, colloidal dispersion stability and thermal stability. Conclusion: The results reflect the potential of TCSCDs for biomedical and pharmaceutical applications.

Exploring the potential of solid dispersion for improving solubility, dissolution & bioavailability of herbal extracts, enriched fractions, and bioactives.

Most drugs' poor aqueous solubility has emerged as a significant challenge in achieving proper therapeutic response following oral administration. Herbal drugs are being used from time immemorial to prevent, mitigate, and cure multiple diseases. However, most of the bioactives phytoconstituents possess limited aqueous solubility & poor oral bioavailability. Solid dispersion (SD) has been realised as an efficient formulation to overcome hydrophobic candidates' solubility issues and improve their oral bioavailability. The current review mainly explores the potential of SD for improving solubility, dissolution & bioavailability of herbal extracts, enriched fractions, and isolated bioactives. Hence, basics of SD, selection of excipients, need for SD of plant products, SD of plant products, selection of preparation method, the chemistry of phytoconstituent-excipient interaction, and hurdles associated with SD of herbal extract/enriched fraction were explored in this review. The SD has the potential to overcome solubility, dissolution, and oral bioavailability issues of poorly soluble phytoconstituents.

Applications of natural product-derived carbon dots in cancer biology.

Natural products have contributed conspicuously to the development of innovative nanomedicines. Hence, the interface between nanomaterial science and plant natural products may bestow comprehensive diagnostic and therapeutic strategies for tackling diseases such as cancer and neurological disorders. Natural product-derived carbon dots (NPdCDs) have revealed noteworthy attributes in the fields of cancer theranostics, microbial imaging, drug sensing and drug delivery. As plants consist of a cocktail of bioactive phytomolecules, the NPdCDs can be anticipated to have medicinal properties, biocompatibility, photo-stability and easy functionalization. NPdCDs have wide-ranging applications. The primary objective of this review is to comment on recent developments in the use of NPdCDs, with special reference to their application in cancer biology. The future of the use of NPdCDs has also been considered.

Multi-Functional Carbon Dots from an Ayurvedic Medicinal Plant for Cancer Cell Bioimaging Applications.

The combination of an Ayurvedic wisdom and nanotechnology may help us to resolve the complex healthcare challenges. A facile and economical one-pot hydrothermal synthesis method has been adopted for preparing a blue fluorescent carbon dots (CDs) with a quantum yield of 15.10% from an Ayurvedic medicinal plant Andrographis paniculata (AP). The Andrographis paniculata derived CDs (AAPCDs) were then characterized using different techniques. Through High Performance Thin Layer Chromatography (HPTLC) profiling of the AP extract and the CDs, it was found that some of the phytoconstituents are retained as such while others may have been converted into their derivatives during the process of formation of CDs. The CDs are designed to possess cellular imaging of human breast carcinoma cells (MCF-7), apart from free radicals sensing and scavenging capabilities. AAPCDs showed minimal cytotoxicity in Multi Drug Resistant clinically isolated strains of gram positive and gram negative bacteria which may be employed for microbiology oriented experiments. These results suggest potential of multi-functional AAPCDs as nano-probes for various pharmaceutical, biomedical and bioengineering applications.

Neurochemical Evidence of Preclinical and Clinical Reports on Target-Based Therapy in Alcohol Used Disorder.

Alcohol use disorder (AUD) is a chronic relapsing disorder, which enforces a person to compulsively seek alcohol, restricting control over alcohol intake leads to emergence of an undesired emotional state during abstinence. There are recent advances for better understanding of neurocircuitry involved in the pathophysiology of AUD. Alcohol interaction with neuronal membrane proteins results in changes in neuronal circuits. It is also linked with the potential medication and their clinical validation concerning their pharmacological targets for alcoholic abstinence. This review covers research work from the past few decades on the therapeutic advances on treatment of alcohol dependence; further detailing the fundamental neurochemical mechanisms after alcohol administration. It also covers interaction of alcohol with GABAergic, glutaminergic, dopaminergic, serotonergic and opioid systems. This review further elaborated the neurobiology of noradrenergic, cholinergic and cannabinoid systems and their interaction with AUD. Elaborative information of potential drug targets under current exploration for AUD treatment with their mechanisms are reported here along with clinical outcomes and the associated side effects.

Di-(2-ethylhexyl) phthalate (DEHP) inhibits steroidogenesis and induces mitochondria-ROS mediated apoptosis in rat ovarian granulosa cells.

Increased oxidative stress (OS) due to ubiquitous exposure to di-(2-ethylhexyl) phthalate (DEHP) can affect the quality of oocytes by inducing apoptosis and hampering granulosa cell mediated steroidogenesis. This study was carried out to investigate whether DEHP induced OS affects steroidogenesis and induces apoptosis in rat ovarian granulosa cells. OS was induced by exposing granulosa cells to various concentrations of DEHP (0.0, 100, 200, 400 and 800 µM) for 72 h in vitro. Intracellular reactive oxygen species (ROS), oxidative stress (OS), mitochondrial membrane potential, cellular senescence, apoptosis, steroid hormones (estradiol & progesterone) and gene expression were analyzed. The results showed that an effective dose of DEHP (400 µg) significantly increased OS by elevating the ROS level, mitochondrial membrane potential, and ß-galactosidase activity with higher mRNA expression levels of apoptotic genes (Bax, cytochrome-c and caspase3) and a lower level of an anti-apoptotic gene (Bcl2) as compared to the control. Further, DEHP significantly (P > 0.05) decreased the level of steroid hormones (estradiol and progesterone) in a conditioned medium and this effect was reciprocated with a lower expression (P > 0.05) of steroidogenic responsive genes (Cyp11a1, Cyp19A1, Star, ERß1) in treated granulosa cells. Furthermore, co-treatment with N-Acetyl-Cysteine (NAC) rescues the effects of DEHP on OS, ROS, ß-galactosidase levels and gene expression activities. Altogether, these results suggest that DEHP induces oxidative stress via ROS generation and inhibits steroid synthesis via modulating steroidogenic responsive genes, which leads to the induction of apoptosis through the activation of Bax/Bcl-2-cytochrome-c and the caspase-3-mediated mitochondrial apoptotic pathway in rat granulosa cells.

Mixed surfactant based (SNEDDS) self-nanoemulsifying drug delivery system presenting efavirenz for enhancement of oral bioavailability.

This study aims to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on non-ionic surfactant mixtures to improve the oral bioavailability of efavirenz (EFZ) categorized as a class II according to the BCS, for HIV- therapy. The result of solubility studies of EFZ in various excipients utilized for construction of the pseudo ternary phase diagram containing surfactant mixtures. Surfactants in 1:1 combination are used with different co-surfactants in different ratio to delineate the area of monophasic region of the pseudo ternary phase diagram. Different accelerated physical stability studies and self-emulsification assessment were performed on the formulations. The formulations clearing the above studies are considered for percentage transmittance and turbidity analysis. The globule size distributions of post diluted SNEDDS having percentage transmittance above 90 were estimated. The TEM analysis of two optimized post diluted SNEDDS formulations further confirm the size in nanometric range (below 50nm). FT-IR studies showed the retention of the characteristic peaks of EFZ in the preconcentrate. The in vitro dissolution profile of SNEDDS established advantages of SNEDDS over plain drug as more than 80% drug was released within 30min in case of optimized SNEDDS while it was approximately 18.3% in the case of plain drug powder. Pharmacokinetic parameters were calculated after performing the in vivo studies of best optimized formulation in rats. The Pharmacokinetic data reveal a 2.63 fold increase in AUC(0-∞) in comparison to plain EFZ suspension. The designed delivery system showed the faith in generating an effective formulation of EFZ for HIV treatment.

Cryptocoryne spiralis, a substitute of Aconitum heterophyllum in the treatment of diarrhoea.

OBJECTIVE: To scientifically validate the traditional substitution of roots of highly expensive Aconitum heterophyllum (AH) with rhizomes of Cryptocoryne spiralis (CS) in the treatment of diarrhoea. METHODS: Different fractions from root/rhizome extract of both the plant were subjected to faecal excretion rate and castor oil-induced diarrhoea models. Further, bioactive fractions from both plants, i.e. chloroform (CAH) from AH at 50 mg/kg p.o. and ethyl acetate (EACS) from CS at 100 mg/kg p.o., were examined for small intestinal transit, intestinal fluid accumulation and PGE2 -induced enteropooling models in rats. Biochemical estimations and Na(+) and K(+) concentration in intestinal fluid were also determined along with antibacterial studies. Phytochemical standardisation of AH and CS was performed by quantifying aconitine for the former and stigmasterol for the latter using HPLC. KEY FINDINGS: CAH and EACS illustrated a significant reduction in faecal output rate and demonstrated a protection of 63.068% at CAH 50 and 59.090% at EACS 100 mg/kg p.o. in castor oil-induced diarrhoea model. The fractions also persuaded promising effects in all the other models, restored alterations in biochemical parameters and showed potential antibacterial activity. CONCLUSION: The antidiarrhoeal potential of AH and CS may be attributed to an antimotility and antisecretory type of effect.

Antidiarrhoeal evaluation of rhizomes of Cryptocoryne spiralis Fisch. ex Wydler: antimotility and antisecretory effects.

The antidiarrhoeal activity of Cryptocoryne spiralis rhizomes extract (250, 500, 750 mg/kg, po) was evaluated using faecal excretion, castor oil-induced diarrhoea, small intestinal transit, intestinal fluid accumulation, gastric emptying and PGE2 induced enteropooling models in rats. In addition, various biochemical estimations, histopathological studies and antibacterial evaluations on strains responsible for diarrhoea were also performed. The results illustrated a significant reduction in normal faecal output rate after 5th and 7th h of treatment, while castor oil-induced diarrhoea model depicted a protection of 55.44% at same dose level from diarrhoea. The other models except, gastric emptying test demonstrated more pronounced effect at same dose level. A significant inhibition in nitric oxide, increase in carbohydrates, protein, DNA, Na(+) and K(+) level with minimum degeneration of colonic fibrous tissues and potent antibacterial activity were also observed. The antidiarrhoeal potential of C. spiralis may be as a result of antimotility and antisecretory type effect mediated through nitric oxide pathway.