Flavonoids containing Vitex negundo extract displayed calcium channels blocking property underlying its anti-diarrheal and anti-spasmodic activities

Diarrhea is a major health problem and despite of interventions, it remains a substantial cause of mortality and morbidity. In this study, a flavonoids-rich Vitex negundo extract was mechanistically evaluated for its effectiveness in diarrheal diseases. The Vitex negundo ethanolic extract was subjected to extraction for isolation of total flavonoids and qualitative phytochemical analysis. The acute toxicity of flavonoids-extract was done in mice to assess its safety and tolerability. The anti-diarrhoeal activity was determined using the castor oil induced diarrhea mouse model at doses of 10, 30 and 100 mg/kg in relation to loperamide (10 mg/kg, oral). The antispasmodic profile was determined by using cut pieces of rabbit’s jejunum in Tyrode’s solutions, employing acetylcholine (0.03μM) as a tissue stabilizer and verapamil, as a calcium channel blocker. The preliminary qualitative analysis of extract revealed different phytochemicals, in addition to flavonoids. The acute toxicity profile showed that the flavonoids-extract is safe and tolerable (LD50 = 1678 mg/kg). In the tissue experiments, the total flavonoids exhibited an EC50 of 1.52 mg/mL and showed maximum relaxation of spontaneous contractions at 5.0 mg/mL and against high-K + induced contractions at 3 mg/mL (EC50 = 0.43 mg/mL). The spasmolytic activity of total flavonoids was comparable to verapamil which suggests that the activity might be due to the blockade of calcium channels. The flavonoids extract (0.1, 0.3 and 1.0 mg/mL) produced an adequate right shift in the calcium concentration response curve as compared to the control (EC50 value = –2.67 mg/mL), which confirmed that the extract has calcium channel blocking activity.

PHYTOCHEMICAL AND PHARMACOLOGICAL PROPERTIES OF FIVE DIFFERENT SPECIES OF JASMINUM

The Genus Jasminum belongs to the family Oleaceae, is widely distributed medicinal plant and has been used since ancient times. The Jasminum species (Jasminum grandiflorum, Jasminum sambac, Jasminum flexile, Jasminum pubescens and Jasminum angustifolium) have been used traditionally as antimicrobial, antiulcerative, antidepressant, anti-inflammatory, anticancerous, flavoring and fragrance agent and for the treatment of breast cancer, diarrhoea, fever, dermatitis, conjunctivitis, abdominal pain, asthma, abscess, uterine bleeding, toothache, headache, insomnia, dysentery and bellyache, diarrhoea and metrorrhagia. The jasmine oil is widely used in aromatherapy. The medicinal properties of Jasminum plants may be due to the presence of a broad spectrum of bioactive compounds such as Phenolics, terpenoids, coumarins, glycosides, steols, esters and fatty acids. The antimicrobial, anti-acne, spasmolytic activity and aromatherapy which is due to the combined effect of essential oils. The phytochemical investigations revealed that phenolic compounds are highly bioactive compared to the majority of terpenoids and other compounds. There are many reports which mentioned the therapeutic potentials of phenolic constituents such as the antioxidant &anti-aging, antiulcer, anti-inflammatory, lipid peroxidation, ACE inhibitor activity, vasodilation effect, wound healing, and protective activity. The present paper reviews the therapeutic potentials of phenolic compounds alongside with the phytoscreening and ethnobotanical aspects of Jasminum.

Cannabinoid Activity—Is There a Causal Connection to Spasmolysis in Clinical Studies?

Cannabinoid drugs are registered for postoperative nausea and emesis, Tourette syndrome and tumor-related anorexia, but are also used for spasticity and pain relief, among other conditions. Clinical studies for spasmolysis have been equivocal and even conclusions from meta-analyses were not consistent. This may be due to uncertainty in diagnostic criteria as well as a lack of direct spasmolytic activity (direct causality). In this review we used the Hill criteria to investigate whether a temporal association is causal or spurious. Methods: A systematic literature search was performed to identify all clinical trials of cannabinoids for spasticity. Studies were evaluated for dose dependency and time association; all studies together were analyzed for reproducibility, coherence, analogy and mechanistic consistency. A Funnel plot was done for all studies to identify selection or publication bias. Results: Twenty-seven studies were included in this meta-analysis. The spasmolytic activity (effect strength) was weak, with a nonsignificant small effect in most studies and a large effect only in a few studies (“enriched” studies, low patient numbers). No dose dependency was seen and plotting effect size vs. daily dose resulted in a slope of 0.004. Most studies titrated the cannabinoid to the optimum dose, e.g., 20 mg/d THC. The effect decreased with longer treatment duration (3–4 months). The spasmolytic effect is consistent for different European countries but not always within a country, nor is the effect specific for an etiology (multiple sclerosis, spinal cord injury, others). For other criteria like plausibility, coherence or analogous effects, no data exist to support or refute them. In most studies, adverse effects were frequently reported indicating a therapeutic effect only at high doses with relevant side effects. Conclusions: Current data do not support a specific spasmolytic effect; a general decrease in CNS activity analogous to benzodiazepines appears more likely. Whether individual patients or specific subgroups benefit from cannabinoids is unclear. Further studies should compare cannabinoids with other, nonspecific spasmolytic drugs like benzodiazepines.

Comparative spasmolytic effect between Cinnamomum tamala and Cinnamomum verum leaf essential oils and eugenol through in vitro and in silico approaches

Cinnamomum tamala and Cinnamomum verum are known for their folk medicinal usage in treating gastrointestinal ailments. The spasmolytic activity of essential oils was studied using isolated rat ileum. The results indicate that C. tamala, despite having a lower content of eugenol (60%), shows a spasmolytic potential of 68.01 ± 2.63% (EC50 = 110.12 ± 13.58 μg/mL) while C. verum with rich eugenol (80%) shows lesser spasmolytic potential (38.96 ± 0.63%) and fails to attain an EC50 value. Upon comparison with standard eugenol’s percentage of spasmolytic (35.68 ± 2.57%), it is evident that the action of these essential oils does not solely rely on the major component but the synergistic role in association with other components of the mixture influences the pharmacological action of the essential oils. In silico docking of phytochemicals of leaf essential oils with M2 (M2AChR) and M3 muscarinic (M3AChR) and nicotinic acetylcholine receptor (nAChR) was carried out to determine the type of receptors through which the essential oils had spasmolytic potential. The binding affinity for eugenol with nAChR shows a better docking score than M2AChR and M3AChR.

An Insight into Endangered Himalayan Paeony (Paeonia emodi royle): Ethnobotany, Phytochemistry and Pharmacology

Paeonia emodi Royle is an endangered herb native to Himalayan region with diverse traditional therapeutic uses. It is categorized as critically endangered plant species. Traditionally plant parts are used for nervous diseases, uterine diseases, dysentery, colic, backache, hypertension, and piles. The medicinal activity is the result of presence of various important phytochemicals triterpenes, monoterpenes, phenolics, lipooxygenases, Nortriprenoids, steroids and aldehydes. P. emodi has many biological activities including antimicrobial, antifungal, anti-toxicity, and spasmolytic activity. Due to remarkable medicinal potential, this species is facing extremely high risk of extinction. This article briefly reviews botanical, medicinal, phytochemical, pharmacological and molecular attributes of this plant species along with its conservation strategies.

Flavonols composition of Ribes nigrum L. juices and their impact on spasmolytic activity

BACKGROUND: Black currants are berries that attract attention due to the beneficial effects they possess. They are proven to be good antioxidants, anticancerogenic, cardio- and neuroprotective agents. OBJECTIVE: The main objective of this research was to evaluate the differences in the flavonols composition, antioxidant and spasmolytic activity of juices obtained from four different black currant cultivars – Triton, Tenah, Ben Sarek, and Ometa, grown over a 4-year long period on the territory of Serbia. METHODS: The qualitative and quantitative determination of black currants juices flavonols was performed using the HPLC. The antioxidative activity was carried out in DPPH and β-carotene systems. The study examined the impact of the main black currants flavonols and black currants juices on the spontaneous, KCl, and acetylcholine-induced ileum smooth muscle contractions. RESULTS: The dominant flavonol in juices of the four different black currant cultivars was myricetin, with its highest content obtained from the 2015 Triton juice (820.1±34.7 μg g–1). Quercetin was the second in abundance and the lowest yields were observed in kaempferol. CONCLUSION: The investigated black currant cultivars were proven to be good sources of flavonols and potential antioxidants with the significant spasmolytic activity that could be successfully used in treating gastrointestinal disorders.

Effects of Funchicórea®, a Traditional Brazilian Herbal Complex, on Intestinal Motility in Healthy and Constipated Rodents

Ethnopharmacological Relevance: The traditional herbal medicinal product Funchicórea® has been widely used in clinical practice for the treatment of intestinal colic and constipation in newborns. However, no scientific data on the herbal product to prove its efficacy is available. Aim of the Study: This study aimed to evaluate the laxative and spasmolytic actions of Funchicórea®. Materials and Methods: Wistar rats (Rattus norvegicus) and Swiss mice (Mus musculus) of both sex, were used. In vivo pharmacological assays were performed to evaluate the stimulating effect on the gastrointestinal tract, and in vitro studies to verify its spasmodic activity. Results: Funchicórea® increased the motility of the small intestine in male mice at doses of 100 mg/kg (161.66±14.86 %, n=6) and 200 mg/kg (151.04±17.17 %, n=6) compared to control (100.00±10.49 %, n=6). However, this drug did not induce any change in intestinal transit in female mice. The intestinal transit of male mice treated with loperamide (3 mg/kg/day, during three days) was reduced 66.25±7.49 % (n=8) compared to the control group (100.00±5.16%, n=8) and we observed the normalization of the intestinal transit in constipated animals treated with Funchicórea® 100 mg/Kg (98.42±6.33 %, and 200 mg/kg (99.32±8.47%, n=7). Similar results were observed in the quantification for 24 hours of male and female rats faeces constipated by loperamide (3 mg/kg/day three days), however, in both animals groups treated with Funchicórea® 100 mg/kg (1.24±2.90 g, male; 3.60±0.80 g, female, n=6) and 200 mg/Kg (8.70±2.01 g, male, 10.03±1.30 g, female, n=6) the levels of faeces returned to basal values compared to constipated group (4.01±1.43 g, male; 1.70±0.10 g, female, n=6). In addition, Funchicórea® (0.01-1000 μg/mL) elicited relaxation in rat ileum pre-contracted by KCl 40 mM (Emax=97.5±7.0 %, n=7) and carbachol (1 μM, Emax=100.0±7.0 %, n=7). Conclusion: The results obtained demonstrated that the herbal medicine Funchicórea® acts by stimulating the intestine of rats and mice and has spasmolytic activity in isolated rat ileum.

Review of Experimental Pharmacological Studies of Plants Used for Asthma Management in Africa

Objectives: The aim was to contribute to the promotion of medicinal plants used in Africa for management of asthma by analyzing their experimental pharmacological evaluation data. Methods: We carried out a systematic review of the literature based on the following research equations in English and in French: « médecine traditionnelle africaine » ET « asthma » ; « African traditional medicine » AND « asthma » or « Medicine African traditional » AND « asthma » ; « plantes médicinales » ET « asthma » ET « antispasmodique » ; «medicinal plants » AND « asthma » AND « anti-spasmodic » ; « plantes médicinales » ET « asthma » ET « anti-inflammatoire » ; «medicinal plants » AND « asthma » AND « anti-inflammatory ». Results: The study revealed 184 medicinal plants used in Africa for the treatment of asthma, 34 of which showed pharmacological properties in favor of their use. In animal experiments, 18 of these plants exerted a spasmolytic effect, 22 an anti-inflammatory effect and 6 both effects. The spasmolytic activity study protocols were based primarily on inhibition of smooth airway muscle contraction, including trachea, induced by various spasmogenic agents. As for of the methods used to study anti-inflammatory activity, the majority of them consisted of tests for carrageenan-induced edema or for formalin-induced leg irritation. Conclusion: Our results justify the need for standardization of experimental study protocols for the recovery of medicinal plants.

Design, synthesis, and spasmolytic activity of thiophene-based derivatives via Suzuki cross-coupling reaction of 5-bromothiophene-2-carboxylic acid: their structural and computational studies

In the current research work, a facile synthesis of a series of novel thiophene-based derivatives of 5-bromothiophene-2- carboxylic acid (1) have been synthesized. All analogs (5a-5e, 10a-10f) were obtained from the coupling reaction of 5-bromothiophene- 2-carboxylic acid (1) and different arylboronic acids with moderate-to-good yields under controlled and optimal conditions. The structures of the newly synthesized compounds were characterized through spectral analysis and their spasmolytic activity, and most of the compounds exhibited potentially good spasmolytic effect. Among the synthesized analogs, compound phenethyl 5-(3,4-dichlorophenyl)thiophene-2-carboxylate (10d) particular showed an excellent spasmolytic effect with an EC50 value of 1.26. All of the compounds were also studied for their structural and electronic properties by density functional theory (DFT) calculations. Through detailed insight into frontier molecular orbitals of the compounds and their different reactivity descriptors, it was found that the compounds 10c and 5c are the most reactive, while 10a is the most stable in the series. Furthermore, compounds 10c and 5c showed a very good NLO response with the highest β values.