Ethnopharmacological basis and pharmacodynamics prospectives for folkloric claims of Rosa webbiana wall. Ex. Royle in diarrhea and asthma via In vitro, In vivo and In silico techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders. AIM OF THE STUDY: This research aimed at multiple targets to verify R. webbiana for treating diarrhea and asthma. In vitro, in vivo, and in silico experiments were planned to demonstrate the antispasmodic and bronchodilator potential of R. webbiana. MATERIALS AND METHODS: The bioactive compounds of R. webbiana were identified and quantified through LC ESI-MS/MS and HPLC. These compounds were predicted for muti-mechanisms of bronchodilator and antispasmodic potential in network pharmacology and molecular docking. In vitro methods (isolated rabbit trachea, bladder, and jejunum tissues) confirmed these multi-mechanisms for antispasmodic and bronchodilator effects. Antiperistalsis, antidiarrheal, and antisecretory experiments were conducted in in-vivo experiments. RESULTS: The phytochemical analysis indicates the presence of rutin (742.91 µg/g), kaempferol (726.32 µg/g), and quercitrin (688.20 µg/g) in Rw. EtOH. These bioactive compounds in network pharmacology interfere with the pathogenic genes of diarrhea and asthma, which are the members of calcium-mediated signaling pathways and showed the stronger binding affinity towards voltage-gated L-type calcium channels, myosin light chain-kinase, Calcium calmodulin-dependent-kinase, Phosphodiesterase-4, and phosphoinositide phospholipase-C in molecular docking. Rw. EtOH elicited a spasmolytic response in isolated jejunum, trachea, and urine preparations by relaxing K+ (80 mM) and CCh (1 µM) spastic contractions. Additionally, it suppressed calcium concentration-response curves to the right, like verapamil. Like dicyclomine, it caused a rightward parallel shift of the CCh curves, followed by a non-parallel shift at higher concentrations with suppression of the maximal response. Like papaverine, it also caused isoprenaline-induced inhibitory CRCs to shift to the left. Verapamil did not potentiate isoprenaline-induced inhibitory CRCs, although it was more efficacious against K+ (80 mM) than CCh (1 µM)-induced contractions. R. webbiana EtOH extract exhibited complete antiperistalsis (21.55%), antidiarrheal (80.33%), and antisecretory (82.59±0.60) activities in vivo experiments at the dose of 300 mg/kg. CONCLUSION: Thus, Rw. EtOH modulated multiple pathways, produced calcium antagonistic, anticholinergic, and phosphodiesterase inhibitory actions, and had antidiarrheal and bronchodilator effects.

Mechanistic insights of Cucumis melo L. seeds for gastrointestinal muscle spasms through calcium signaling pathway-related gene regulation networks in WGCNA and in vitro, in vivo studies.

BACKGROUND: In addition to the nutritional benefits of Cucumis melo L., herbalists in Pakistan and India employ seeds to treat various ailments. This study aimed to determine the regulatory role of C. melo seeds in calcium-mediated smooth muscle contraction. METHODS: We identified and quantified the phytochemicals of C. melo with LC ESI-MS/MS and HPLC, then conducted in vitro and in vivo tests to confirm the involvement in smooth muscle relaxation. Then, diarrhea-predominant irritable bowel syndrome gene datasets from NCBI GEO were acquired, DEGs and WGCNA followed by functional enrichment analysis. Next, molecular docking of key genes was performed. RESULTS: The quantification of C. melo seeds revealed concentrations of rutin, kaempferol, and quercetin were 702.38 µg/g, 686.29 µg/g, and 658.41 µg/g, respectively. In vitro experiments revealed that C. melo seeds had a dose-dependent relaxant effect for potassium chloride (80 mM)-induced spastic contraction and exhibited calcium antagonistic response in calcium dose-response curves. In in vivo studies, Cm.EtOH exhibited antidiarrheal, antiperistaltic, and antisecretory effects. The functional enrichment of WGCNA and DEGs IBS-associated pathogenic genes, including those involved in calcium-mediated signaling, MAPK cascade, and inflammatory responses. MAPK1 and PIK3CG were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. CONCLUSIONS: The bronchodilator and antidiarrheal effects of C. melo were produced by altering the regulatory genes of calcium-mediated smooth contraction.

Possible Mechanisms Underlying the Antispasmodic, Bronchodilator, and Antidiarrheal Activities of Polarity-Based Extracts of Cucumis sativus L. Seeds in In Silico, In Vitro, and In Vivo Studies.

Apart from the nutritional value, Cucumis sativus L. has also been used in the traditional medicine of Iran, Pakistan, and India. Its seeds are used by herbalists to treat gastrointestinal, respiratory, and urinary problems. However, more investigations are required to explain its mechanisms for treating GI, respiratory, and urinary diseases. Accordingly, the aim of the present work was to investigate the antispasmodic, bronchodilator, and antidiarrheal activities of C. sativus seeds extracts and the underlying mechanisms of action. For this purpose, sequential extracts of C. sativus seeds were prepared in n-hexane, dichloromethane, ethanol, and water. Bioactive compounds in C. sativus seed extracts were identified and quantified by utilizing LC ESI-MS/MS and HPLC. Moreover, network pharmacology and molecular docking were employed to examine the antispasmodic and bronchodilator effects of the bioactive substances in the extracts. In vitro and in vivo experiments were also conducted to validate the mechanistic insights gained from the in silico analysis. Results indicated the presence of kaempferol with a concentration of 813.74 µg/g (highest concentration) in the seed extract of C. sativus, followed by quercetin (713.83 µg/g), narcissin (681.87 µg/g), and orientin (676.19 µg/g). In silico investigations demonstrated that the bioactive chemicals in C. sativus seeds inhibited the expression of the target genes involved in smooth muscle contraction and calcium-mediated signaling. Sequential seed extracts of C. sativus caused a dose-dependent relaxant response for spasmolytic reaction and resulted in a relaxation of K+ (80 mM) spastic contraction. In animal models, C. sativus seed extracts exhibited partial or complete antiperistalsis, antidiarrheal, and antisecretory actions. By modulating the contractile response through calcium-mediated signaling target proteins, C. sativus seeds generated bronchodilator, antispasmodic, and antidiarrheal therapeutic effects.

Antispasmodic activity of the ethanol extract of Citrullus lanatus seeds: Justifying ethnomedicinal use in Pakistan to treat asthma and diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus lanatus (Thunb.) belongs to the ground family, Cucurbitaceae, known for edible fruit. Besides nutritional benefits, the traditional herbal practitioners in Pakistan and India used their seeds to treat gastrointestinal, respiratory, and urinary disorders. In Northern Sudan, its seeds are often used as a laxative. Its root is laxative and emetic at a high dose. Its seeds are also used to treat bedwetting and urinary tract obstruction. AIM OF THE STUDY: This study aimed to elucidate the multi-target mechanisms of Citrullus lanatus seeds to treat asthma and diarrhea. The pharmacological experiments were designed and conducted, along with the pharmacology network and molecular docking predictions, to verify the seeds biopotency for antispasmodic and bronchodilator properties. METHODS: LC ESI-MS/MS were performed to identify the potentially active compounds in hydroethanolic extract of Citrullus lanatus seeds, then to quantify them by HPLC. The quantified bioactive compounds of Citrullus lanatus, i.e., stigmasterol, quinic acid, malic acid, epicatechin, caffeic acid, rutin, p-coumaric acid, quercetin, ferulic acid, scopoletin, apigenin, and kaempferol were subjected to in silico studies for molecular docking. The hydroethanolic extract of Citrullus lanatus seeds was examined on isolated rabbit tissue, i.e., jejunum, trachea, and urinary bladder. The antiperistalsis, antidiarrheal and antisecretory studies were also performed in animal models. RESULTS: In silico studies revealed that bioactive compounds of C. lanatus seeds interfere with asthma and diarrhea-associated target genes, which are a member of calcium mediate signaling, regulation of cytosolic calcium concentration, smooth muscle contraction, and inflammatory responses. It was also found that rutin, quercetin, kaempferol, and scopoletin were stronger binding to voltage-gated calcium channels, calcium/calmodulin-dependent protein kinase, myosin light chain kinase, and phosphoinositide phospholipase C, thus, exerting calcium channel blocker activity. The hydroethanolic extract of C. lanatus seeds exerted a concentration-dependent relaxant response for the spasmolytic response on isolated jejunum and trachea preparations and caused relaxation of spastic contraction of K+ (80 mM). Furthermore, it caused a non-parallel rightward shift with suppression of calcium concentration-response curves. In animal models, the Cl.EtOH showed antiperistalsis, antidiarrheal and antisecretory response. CONCLUSION: Thus, we confirm Citrullus lanatus seeds have some medicinal effects by regulating the contractile response through target proteins of calcium mediates signaling and can be a promising component in the medical treatment for asthma and diarrhea.

Metabolomics based mechanistic insights to vasorelaxant and cardioprotective effect of ethanolic extract of Citrullus lanatus (Thunb.) Matsum. & Nakai. seeds in isoproterenol induced myocardial infraction.

BACKGROUND: Cardiovascular diseases (CVDs) are a significant cause of morbidity and death in the current world, posing a challenge to both developing and industrialized nation's health systems. Citrullus lanatus (Thunb.) Matsum. & Nakai. seeds have long been utilized to supplement and enhance health and treat cardiovascular illnesses. However, its treatments for CVDs are still unknown. More research is required to fully comprehend the impact of C. lanatus seeds on vasorelaxation and myocardial infractions. PURPOSE: Therefore, an integrated metabolomics profiling technique was used to investigate possible pathways of C. lanatus in isoproterenol (ISO)-induced myocardial infarction (MI). Isoproterenol causes long-term cardiac hypertrophy by causing cardiomyocyte compensatory loss, eventually leading to heart failure. METHODS: In vitro models of vasoconstriction, atrium, and in vivo models of invasive blood pressure measurement and isoproterenol (ISO) induced cardiac hypertrophy in rats were used to understand underlying mechanistic by LC-MS/MS based dynamic metabolomics analysis of the serum and heart samples to be investigated the effect of ethanolic extract of C. lanatus (Cl.EtOH). RESULTS: Cl.EtOH exhibited vasorelaxant, negative chronotropic, and inotropic effects in in-vitro models whereas, a potent hypotensive effect was observed in normotensive rats. The Cl.EtOH protected the animals from ISO-induced myocardial infarction (MI) with therapeutic interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, biochemical assays, and metabolomic profiling of serum and heart tissues. CONCLUSIONS: For the first time, our study confirmed that C. lanatus seeds (Cl.EtOH) possess significant antihypertensive and prevent ISO-induced myocardial infarction. These findings comprehensively demonstrated mechanistic insights of Cl.EtOH in vasorelaxation and myocardial infarction. The current study provides evidence for further mechanistic studies and the development of C. lanatus seeds as a potential therapeutic intervention for patients with cardiovascular disorders.

Scientific basis for medicinal use of Citrullus lanatus (Thunb.) in diarrhea and asthma: In vitro, in vivo and in silico studies.

BACKGROUND: Citrullus lanatus (Thunb.) is a member of the Cucurbitaceae family, commonly farmed as an edible vegetable around the globe. It has been used in traditional therapies in addition to nutritional advantages. Traditional herbal practitioners employ C. lanatus seeds to treat gastrointestinal, respiratory, and urinary diseases in Pakistan and India. However, more investigation is needed to understand the effect of C. lanatus seeds on treating gastrointestinal, respiratory, and urinary disorders. PURPOSE: This research aimed to use network pharmacology and molecular docking to understand multi-target mechanisms of C. lanatus seeds against asthma and diarrhea and to validate its effects using biological tests to investigate antispasmodic and bronchodilator capabilities. METHODS: The ground seeds of C. lanatus were extracted in hexane, dichloromethane, ethanol, and aqueous for sequential extracts. The bioactive components in sequential extracts of C. lanatus seeds were identified using LC ESI-MS/MS, and specific compounds were quantified using HPLC. The quantified bioactive compounds of C. lanatus were subjected to in silico studies for network pharmacology and molecular docking to elucidate their role in antispasmodic and bronchodilator properties. The sequential extracts were tested on isolated rabbit tissue, i.e., jejunum, trachea, and urinary bladder. The antiperistalsis, antidiarrheal and antisecretory studies were also performed in animal models. RESULTS: In silico studies indicate that bioactive chemicals from sequential extracts of C. lanatus seeds interfere with asthma and diarrhea-associated pathogenic genes. Those are members of calcium mediate signaling, cholinergic synapse, regulation of cytosolic calcium concentration, smooth muscle contraction, and inflammatory responses. It was also found that rutin, quercitrin, stearic acid, umbelliferone, and kaempferol were stronger binding to voltage-gated calcium channels and muscarinic M3 receptor, thus exerting calcium channel blocker activity and cholinergic receptor stimulant response. On isolated jejunum, trachea, and urinary preparations, sequential extracts of C. lanatus seeds elicited the spasmolytic response and showed the relaxation of spastic contractions of K+ (80 mM) and carbachol (1 µM). Furthermore, it induced a non-parallel rightward shift in calcium concentration-response curves with suppression. In animal models, C. lanatus seed extracts exhibited partially or completely antiperistalsis, antidiarrheal, and antisecretory effects. CONCLUSION: Thus, Citrullus lanatus had therapeutic benefits by modulating the contractile response through calcium-mediated signaling target proteins, hence exerting bronchodilator and antidiarrheal properties. The current study provides evidence for further mechanistic studies and the development of C. lanatus seeds as a potential therapeutic intervention for patients with gastrointestinal, respiratory, and urinary disorders.

Metabolomics analysis delineates the therapeutic effects of hydroethanolic extract of Cucumis sativus L. seeds on hypertension and isoproterenol-induced myocardial infarction.

Cucumis sativus L., widely cultivated as an edible vegetable. Its seeds are well reputed for cardiovascular preventive properties. However, the mechanisms underlying for cardiovascular protection of C. sativus are still unidentified. Therefore, this study utilized a metabolomics approach to investigate putative mechanisms of C. sativus seeds in myocardial infarction (MI) and in vitro models of vasoconstriction, atrium, and invasive blood pressure measurement. Results showed that Cu.EtOH extract showed a vasorelaxant response with potent hypotensive effect in normotensive rats and L-NAME induced hypertension. Cu.EtOH caused a negative inotropic and positive chronotropic effect on the atrium. Cu.EtOH protected the animals from ISO-induced myocardial infarction (MI) interventions in left ventricular thickness, cardiomyocyte hypertrophy, mRNA gene expression, and biochemical assays. The metabolomics data suggested that Cu.EtOH mainly affected amino acid metabolism, BCAA degradation, ketone bodies degradation, and oxidative stress. Our study showed that Cu.EtOH suppressed inflammation with a strong anti-myocardial infarction impact. Additionally, our findings indicated Cu.EtOH reverted the amino acid metabolism, BCAA, and ketone bodies degradation. The findings show the antihypertensive mechanism of Cu.EtOH may include the modulation of endothelium-derived relaxing factor (EDRF) produced from nitric oxide (NO) and is connected with vascular endothelial function. C. sativus seeds, in particular, played a pivotal role in the treatment of myocardial and vascular disorders by enhancing the EDRF mechanism, energy generation, and antioxidant capacity. In summary, our findings showed the mechanistic insights on the therapeutic potential of C. sativus seeds for cardiovascular disorders.

Cardioprotective, hypotensive and toxicological studies of Populus ciliata (Wall. ex Royle).

Populus ciliata Wall ex. Royle has folkloric repute to treat various cardiovascular ailments and related disorders. The current study was designed to evaluate the toxic profile, cardioprotective and hypotensive effects of Populus ciliata (Wall. ex Royle). Populus ciliata crude ethanolic extract (Pc. Cr) and its aqueous (Pc. Aq) & organic (Pc. Dcm) fractions were tested on isolated aorta of rat and rabbit having intact and non-intact endothelium respectively. Pc. Cr & Pc. Aq relaxed the contractions induced by PE (1 µM)-induced and K+ (80 mM)-induced on aorta, possibly by mediating endothelium derived relaxing factor (EDRF) in intact endothelium and voltage dependent L-type calcium channels blocking (CCB) mechanism in non-intact endothelium. Pc. Cr showed anti-hypertensive & cardioprotective activity by decreasing force of contraction & heart rate on isolated rabbit paired atria and reduced blood pressure in anesthetized rat. Cardioprotective effect of Pc. Cr was assessed in isoproterenol induced acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) in Sprague Dawley rats. In LVH, Pc. Cr exerted positive effects by decreasing angiotensin II & renin and increasing cGMP & nitric oxide (NO) with reduced cardiac fibrosis, necrosis and cardiac cell size. In AMI, Pc. Cr responded effectively by decreasing cardiac markers creatinine kinase (CK), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LD) in blood associated with less edema and necrosis. Presence of catechin, vinallic acid, P-coumeric acid and quercitin identified through HPLC support the effectiveness of Pc. Cr in hypertension, AMI and LVH. Pc. Cr showed no significant adverse effects in Sprague Dawley albino rats after acute & sub-acute treatment in histopathological investigation. Extract of Populus ciliata showed vasorelaxant, hypotensive and cardioprotective effect in Sprague Dawley albino rats and white albino rabbit by mediating EDRF and voltage dependent L-type CCB mechanism respectively.

The genus Cassia L.: Ethnopharmacological and phytochemical overview.

Nature gifts medicinal plants with the untapped and boundless treasure of active chemical constituents with significant therapeutic potential that makes these plants a beneficial source in the development of phytomedicines. Genus Cassia, with approximately 500 species, is a large group of flowering plants in the family Fabaceae. Cassia species are widely distributed throughout different regions mainly tropical Asia, North America, and East Africa. In the folk medicinal history, these plants are used as laxative and purgative agents. In the Ayurveda system of medicine, they are used to cure headache and fever. Cassia plants exhibit pharmacological activities at large scales such as antimicrobial, anticancer, antiinflammatory, antioxidant, hypoglycemic, hyperglycemic, antimutagenic, and antivirals. The phytochemical investigations of genus Cassia demonstrate the presence of more than 200 chemical compounds, including piperidine alkaloids, anthracene derivatives (anthraquinones), flavonoids, pentacyclic triterpenoids, sterols, phenylpropanoids, and γ-naphthopyrones. The literature illustrated anthraquinones and flavonoids as major secondary metabolites from this genus. However, some Cassia plants, with rich contents of anthraquinones, still show toxicology properties. As Cassia plants are used extensively in the herbal system of medicine, but only senna dosage forms have achieved the status of the pharmaceutical market as standard laxative agents. In conclusion, further investigations on isolating newer biologically active constituents, unknown underlying mechanisms, toxicology profiles, and clinical studies of Cassia species are needed to be explored. This review article specifies the systematic breach existing between the current scientific knowledge and the fundamentals for the marketization of genus Cassia products.

Ethnopharmacological basis for folkloric claims of Anagallis arvensis Linn. (Scarlet Pimpernel) as prokinetic, spasmolytic and hypotensive in province of Punjab, Pakistan.

ETHNOPHARMACOLOGICAL RELEVANCE: The conventional naturopaths of Punjab Province (Pakistan) have trivial usage of Anagallis arvensis Linn.(Primulaceae) for cure of diarrhea, constipation, asthma as well as hypertension. AIM: Present research was focused to discover comprehensive mechanism of spasmogenic, spasmolytic, bronchorelaxant and hypotensive folkloric usage of Anagallis arvensis Linn.. METHODOLOGY: The crude extract of Anagallis arvensis Linn. (Aa.Cr) & its (aqueous & organic) portions tested in-vitro on isolated jejunum, ileum, trachea, aorta, paired atria preparations as well as in-vivo in mice & normotensive anaesthetized rats. The responses have been noted by transducers (isotonic & isometric) coupled to Power Lab. RESULT: Anagallis arvensis Linn. (Aa.Cr; crude aqueous-alcoholic extract) produced contractile action at low concentrations but relaxant action was observed by increasing concentrations on spontaneous contractions of isolated jejunum of rabbit. But, pre-treatment of tissue with atropine prior extract caused suppression of contractile effect indicating presence of cholinergic muscarinic response of Aa.Cr. It also triggered relaxation of high Potassium -stimulated contractions of jejunum with subsequent non-parallel right move in Ca++ CRCs. Moreover, Aa.Cr relaxed carbachol - & high Potassium - stimulated contractions in trachea of rabbit but observed relaxant effect was powerful against CCh (1 µM)- stimulated contractions with rightside parallel move of CCh-curves succeeded by non-parallel move, like Dicyclomine, having dual activities. The Aa.Cr also showed relaxant result on Phenylephrine and High Potassium -prompted contractions in endothelium intact aorta. The fractionation revealed segregations of contractile & relaxant effects in relevant aqueous & organic portions. The Intravenous administration of Aa.Cr to ketamine-diazepam anaesthetized normo-tensive albino rats resulted in decreased MABP, SBP & DBP. The Aa.Cr applied negative (-) inotropic & chronotropic action on paired atria. The Aa.Cr also exhibited anti-diarrheal action in mice against castor oil prompted diarrhea and also mitigated distance covered by charcoal meal in gastrointestinal tract in a manner comparable with loperamide. CONCLUSION: These results revealed presence of CCB and selective muscarinic agonist activity in Aa.Cr, hence validating folkloric practice of Anagallis arvensis Linn. in diarrhea, constipation, asthma & hypertension.

Studies to Elucidate the Mechanism of Cardio Protective and Hypotensive Activities of Anogeissus acuminata (Roxb. ex DC.) in Rodents.

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases.

Ex vivo and in vivo studies of Viola tricolor Linn. as potential cardio protective and hypotensive agent: Inhibition of voltage-gated Ca++ ion channels.

Viola tricolor Linn. is used as cardio-protective and anti-hypertensive agent in traditional medicine. Current study objective was to evaluate cardio-protective and hypotensive effects of Viola tricolor L. in vitro and in vivo studies. Viola tricolor L. crude extract (Vt.Cr) and its fractions (Aqueous and organic) were tested at rabbit atria and aorta coupled to Power Lab Data Acquisition System for cardio depressant and vasorelaxant effects in vitro whereas in vivo Blood Pressure was checked by invasive method in normotensive ketamine-diazepam anesthetized rats. Isoproterenol was employed for acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) development and cardioprotective effects of Vt.Cr were evaluated hemodynamically and histopathologically. Vt.Cr and its fractions decreased heart rate and contractile force in paired atria and relaxed Phenylephrine (1 µM) and K+ (80 mM) stimulated contractions in aorta possibly mediated through Voltage dependent L-type calcium channels blockage supported by in vivo hypotensive action. In LVH, Vt.Cr lowered Angiotensin Converting Enzymes and renin, increased cyclic Guanosine Monophosphate and nitric oxide levels, decreased cardiomyocytes size and fibrosis attributed to Gallic acid as detected by High Performance Liquid Chromatography. Partial positive results were seen hemodynamically and histologically in AMI Viola tricolor L. showed vasorelaxant, cardio-relaxant, hypotensive, and cardio protective effect validating traditional practice in cardiovascular disorders.

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.

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.

Evaluation of smooth muscle relaxant potential of Bismarckia nobilis (Hildebr. & Wendl.) in diarrhea, hypertension and asthma by ex-vivo and in-vivo method / Evaluación del potencial relajante en músculo liso de Bismarckia nobilis (Hildebr. & Wendl.) en diarrea, hipertensión y asma por métodos ex vivo e in vivo

To explore the mechanistic basis behind smooth muscle relaxant prospective of Bismarckia nobilis in gastrointestinal, respiratory and cardiovascular ailments. The methanolic extract of B. nobilis and sub-fractions have been evaluated in vitro rabbit isolated tissues, in vivo castor oil-induced diarrhea in rats and charcoal meal activity in mice. The B. nobilis extract relaxed spontaneous and K+(80 mM)- induced contractions in rabbit isolated jejunum preparations, CCh (1 µM) and K+ (80 mM)-induced contractions in tracheal and bladder preparations, PE (1 µM) and K+ (80 mM)-induced concentrations in aorta preparations, likewise verapamil. Spasmolytic activity of dichloromethane fraction is stronger as compared to aqueous fraction. In vivo castor oil-induced diarrhea in rats and charcoal meal activity in mice further supported spasmolytic activity. B. nobilis extract possess anti-spasmodic, anti-diarrheal, airway relaxant and vasodilator activities possible mediated through calcium channel blocking mechanism, justifying therapeutic utility of B. nobilis in diarrhea, asthma and hypertension.

El objetivo de trabajo fue explorar el mecanismo de acción relacionado con el efecto relajante del músculo liso inducido por Bismarckia nobilis (B. nobilis) en enfermedades gastrointestinales, respiratorias y cardiovasculares. El extracto metanólico de B. nobilis y subfracciones fue evaluado in vitro en tejidos aislados de conejos. Además se evaluó diarrea in vivo inducida con aceite de ricino en ratas y la actividad de harina de carbón vegetal en ratones. El extracto de B. nobilis relajó tanto las contracciones espontáneas como las inducidas por K+(80 mM) en preparaciones de yeyuno aisladas de conejos, las contracciones inducidas por PE (1 µM) y K+(80 mM) inducidas en preparaciones de aorta; de manera similar a verapamilo. La actividad espasmolítica de la fracción de diclorometano es más potente en comparación con la fracción acuosa. La diarrea inducida in vivo por el aceite de ricino en ratas y la actividad de la harina de carbón vegetal en ratones apoyaron aún más la actividad espasmolítica. El extracto de B. nobilis posee actividades antiespasmódicas, antidiarreicas, relajantes de las vías respiratorias y vasodilatadoras, posibles a través del mecanismo de bloqueo de los canales de calcio, lo que justifica la utilidad terapéutica de B. nobilis en la diarrea, el asma y la hipertensión.

Diuretic and serum electrolyte regulation potential of aqueous methanolic extract of Solanum surattense fruit validates its folkloric use in dysuria.

BACKGROUND: Solanum surattense Burm. (Solanaceae) is traditionally used for management of various ailments. The study was conducted for provision of pharmacological justification for folkloric uses of Solanum surattense in the treatment of dysuria. METHODS: Rats were randomly divided into 5 groups, each of (n = 6). Aqueous methanolic fruit extract of S. surattense were also administered intraperitoneally to the rats at doses of 50, 70 and 100 mg/kg. Furosemide (10 mg/kg i.p) was used as standard drug whereas controls were given saline solution (40 mL/kg i.p). The electrolytes in urine were measured using a flame photometer whereas serum sodium, potassium, calcium, bicarbonate and blood urea nitrogen (BUN) were determined by using an automatic analyzer. Urine osmolality was assayed by the micro-osmometer. RESULTS: The extract S. surattense induced diuretic effects in a dose-dependent manner as compared with control. Upon administration of extract (70 and 100 mg/kg), we observed the prominent (p < 0.01) increase in the urine volume and osmolality in comparison to control group. However, plant extract (100 mg/kg) significantly increase the urinary electrolyte excretion especially calcium (p < 0.05) to that of the furosemide whereas level of magnesium remains constant. Moreover, our results showed a decrease in serum levels of sodium, potassium, calcium and blood urea nitrogen (BUN), but concentration dependent increase in bicarbonate was found in the test groups. There was no substantial change in the pH of urine samples of the extract-treated groups. CONCLUSION: These results indicate that S. surattense investigated exert its action by causing diuresis in the treatment of dysuria.

Rationalizing ethnopharmacological uses of Alternanthera sessilis: A folk medicinal plant of Pakistan to manage diarrhea, asthma and hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Tribal herbal practitioners of Pakistan use Alternanthera sessilis (Amaranthaceae) to treat diarrhea, asthma and hypertension. OBJECTIVE: The current study was conducted to provide mechanistic basis for anti-spasmodic, anti- asthmatic and anti-hypertensive use of Alternanthera sessilis. MATERIALS AND METHODS: The crude ethanolic extract of Alternanthera sessilis (As.Cr) and its fractions were tested in- vitro on isolated rabbit tissue preparations (i.e., jejunum, trachea, and aorta) and in-vivo in ketamin-diazepam anaesthetized normotensive rats.The responses were recorded using isotonic and isometric transducers coupled with Power Lab data acquisition system. RESULTS: On isolated rabbit jejunum preparations, As.Cr exerted concentration-dependent (0.01-1.0mg/ml) spasmolytic effect and caused relaxation of K(+)(80mM)-induced spastic contractions. Furthermore, there was non-parallel shift in Ca(++)concentration response curves (CRCs) towards right at tissue bath concentrations of 0.1 and 0.3mg/ml. On isolated rabbit trachea, it relaxed carbachol (1µM)- and K(+()80mM)-induced contractions at respective tissue bath concentrations of 5.0 and 1.0mg/ml. On isolated rabbit aorta, it also demonstrated relaxant effect on phenylephrine (1µM)- and K(+()80mM)-induced contractions at tissue bath concentrations of 5.0 and 3.0mg/ml respectively. These findings were found to be comparable with verapamil, a reference Ca(++)channel blocker (CCB). The solvent-solvents fractionation revealed domination of spasmolytic effects in dichloromethane fraction as compared to aqueous fraction. Intravenous administration of As.Cr decreased mean arterial blood pressure, systolic blood pressure and diastolic blood pressure of ketamine-diazepam anaesthetized normotensive albino rats dose-dependently, at dose range of 1-10mg/kg. CONCLUSION: Our results reflected presence of Ca(++) channel blocking (CCB) activity in As.Cr, thus rationalizing medicinal use of Alternanthera sessilis in diarrhea, asthma and hypertension.

Validation of ethnopharmacological uses of Murraya paniculata in disorders of diarrhea, asthma and hypertension.

BACKGROUND: Murraya paniculata is traditionally used for management of gut, air way and cardiovascular disorders. The study was conducted for provision of pharmacological rationalization for folkloric uses of Murraya paniculata in gut, air way and cardiovascular problems. METHODS: Aqueous-ethanolic extract of Mp.Cr was tested using in vitro techniques on isolated tissue of rabbit (jejunum, trachea and aorta) to detect the possible presence of spasmolytic activity. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system. RESULTS: Application of the extract of Mp.Cr relaxed spontaneous and high K(+) (80mM)-induced contraction in rabbit jejunum preparation. Because it shifted the CRCs (Calcium response curve) towards the right side so the possible blockade was of calcium channel similar to verapamil. In rabbit trachea, extract of Mp.Cr produced relaxation of carbachol and high K(+) induced contractions. When plant extract was checked further on isolated aorta for its possible vasodilator effect, it caused relaxation of phenylephrine and high K(+)-induced spastic contractions at different doses. CONCLUSION: These results indicate that Murraya paniculata shows anti-spasmodic, bronchodilator and vasodilator activity facilitated through Ca(++) antagonist mechanisms.

Validation of ethnopharmacological uses of Heliotropium strigosum Willd. as spasmolytic, bronchodilator and vasorelaxant remedy.

BACKGROUND: Heliotropium strigosum is used in traditional medicine to manage gastrointestinal pain, respiratory distress and vascular disorders. The present study was undertaken to provide scientific evidences for these folkloric uses by in vitro experimental settings. METHODS: A crude methanol extract of the Heliotropium strigosum (Hs.Cr) was tested in vitro on isolated rabbit jejunum preparations to detect the possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. RESULTS: The Hs.Cr exhibited relaxant effects in rabbit jejunum in a concentration dependent manner (0.01-3.0 mg/ml). The Hs.Cr also relaxed K(+) (80 mM)-induced spastic contractions in rabbit jejunum and shifted the Ca(2+) concentration response curves towards right. The extract relaxed carbachol (1 µM)- as well as K(+) (80 mM)-induced contractions in rabbit trachea at concentrations ranging from 0.01 to 10 mg/ml. Moreover, Hs.Cr. also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 µM)- and K(+) (80 mM)-induced contractions in isolated rabbit aorta. CONCLUSIONS: The Hs.Cr was found to exhibit spasmolytic, bronchodilator and vasorelaxant activities on isolated rabbit jejunum, trachea and aorta preparations, likely mediated through Ca(2+) channel blockade. This finding may provide a scientific basis for the folkloric uses of the plant.

Pharmacological justification of use of Solena heterophylla Lour. in gastrointestinal, respiratory and vascular disorders.

BACKGROUND: Solena heterophylla Lour. has traditionally been used in the management of diseases pertaining to gastrointestinal, respiratory and vascular system and present study was undertaken to validate its traditional uses. METHODS: The aqueous ethanolic extract of Solena heterophylla Lour (Sh.Cr) was tested in-vitro on isolated rabbit jejunum, tracheal and aorta preparations. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system. RESULTS: The aqueous ethanolic extract of Solena heterophylla Lour (Sh.Cr) (0.03-1.0 mg/ml) on application to spontaneous contractions in isolated rabbit jejunum preparation exerted relaxant effect through decrease in magnitude and frequency of contractions, caused relaxation of K(+)(80 mM)-induced contractions and shifted the Ca(2+) concentration response curves toward right in isolated rabbit jejunum preparations in a manner similar to verapamil (a standard Ca(2+) channel blocker), thus confirming its Ca(2+) channel blocking activity. The Sh.Cr also caused relaxation of carbachol (1 µM)- and K(+)(80 mM)-induced contractions in isolated rabbit tracheal preparations in a manner comparable to dicyclomine. CONCLUSIONS: The observed relaxant effect may be outcome of anti-muscarinic and Ca(2+) channel blocking activities. The Sh.Cr (0.03-1.0 mg/ml) against phenyephrine (1 µM)- and K(+)(80 mM)-induced contractions in isolated rabbit aortic preparations exerted a relaxant effect, possibly through Ca(2+) channel blocking activity. These findings provide a rationale for the folkloric uses of the plant in the management of ailments pertaining to gastrointestinal, respiratory and vascular system.