Cytotoxicity and Sedative Activity of Steam Bark of Dillenia indica L.

The study aims to assess the cytotoxic activity of the methanolic extract (CME) and various fractions from the bark of Dillenia indica L (Family: Dilleniaceae) using brine shrimp lethality bioassay and sedative activities using hole cross, open field, and elevated-plus maze (EPM) test in Swiss albino mice. In brine shrimp assay, the LC50 for CME, pet-ether (PETF), chloroform (CHF) and aqueous (AQF) fraction were found to be 110, 24.55, 85 and 14.45 μg/ml, respectively, indicating significant cytotoxicity of PETF and AQF when compared to the standard vincristine sulfate (7.5 μg/ml). In open field test, the number of movements per min (after 120 min) was 40.90, 12.43, 5.45, 3.66, and 29.74 for control, standard diazepam, CME, CHF and AQF, respectively, indicating strong activity of the chloroform soluble fraction compared to the other test samples of D. indica. Similar data was observed in hole cross test where the number of movements per minute after 120 min were 3.60, 5.56, 4.77, and 7.99 for the standard, CME, CHF and AQF, respectively. In EPM test, the CME showed a significant decreased percentage of entries of mice into the open arms of EPM as well as the percentage of time spent in the open arms. The result indicates that the CHF significantly suppressed the locomotor activity than that of methanol and aqueous fractions. These findings will be helpful for bioassay-guided isolation of active principles responsible for cytotoxicity and sedative activities. Bangladesh Pharmaceutical Journal 24(2): 105-110, 2021

Essential Oil from the Leaves of Chromolaena odorata, and Sesquiterpene Caryophyllene Oxide Induce Sedative Activity in Mice

Chromolaena odorata (L.) R.M.King & H.Rob. essential oil (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and the most efficient concentrations were 0.04 and 0.00004 mg/cage (volume of the cage 61.2L). Analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound and bioactivity-guided fractionation of the oil was performed to isolate the compound responsible for activity. The data clearly identified sesquiterpene caryophyllene oxide as the compound inducing COEO sedative activity and it was effective in decreasing mice locomotor activity by 56% and 57% at 0.0004 and 0.04 mg/cage, respectively. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the central nervous system (CNS) by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results showed that caryophyllene oxide is a potent CNS depressant. Nevertheless, it fails to potentiate the effects of pentobarbital on the GABAergic system, nor did flumazenil, a GABAA receptor antagonist, reversed its effects. It was especially interesting to note that β-caryophyllene, the precursor of caryophyllene oxide, demonstrated a similar pattern of sedative activity, and the present work further extends actual knowledge on these naturally occurring sesquiterpenes. The findings in this study reveal the new activity of caryophyllene oxide as an innovative way to manage sleep and CNS-related disorders, and demonstrates a satisfactory effect of two interesting sesquiterpene compounds on the CNS.

STUDYING SEDATIVE ACTIVITY OF COMBINED TINCTURE OF MOTHERWORT AND ST JOHN'S-WORT

The paper presents studying sedative activity of the combined tincture of motherwort and St. John's wort. The combined tincture of motherwort and St. John's wort was obtained by percolation method in a ratio 1:10. Standardization of the obtained tincture was carried out with quality indicators: description, content of active ingredients and ethanol, relative density, dry residue. According to all quality indicators, the tincture obtained met the requirements of the State Pharmacopoeia of the Republic of Belarus. Specific sedative activity of the combined tincture of motherwort and St. John's wort was assessed by barbiturates hypnotic effect prolongation (sodium thiopental), by the rate of falling asleep in animals and by animals staying in lateral position in relation to the control group to which sodium thiopental was injected. In the studies carried out it was found that injection of the combined tincture of motherwort and St. John's wort at a dose of 0,1 ml / kg increases sleep by 125,63% and also accelerates the process of falling asleep by 327,75% compared with the separate injection of motherwort and St. John's wort tincture at doses of 0,1 ml/kg. It was shown that the injection of the combined tincture of motherwort and St. John's wort at a dose of 0,1 ml/kg exhibits a potentiated effect and enhances the hypnotic effect of sodium thiopental administered at a dose of 10 mg/kg.

Evaluation of Antidiabetic, Antidiarrheal and Sedative Effects of the Methanolic Extract of Clerodendrum viscosum Roots in Mice

Background: Clerodendrum viscosum is one of the most well-known plants in traditional practices. The study aims to explore the antidiabetic, antidiarrheal and sedative effects of methanolic extract of Clerodendrum viscosum roots (MECV) in mice. Methods: For each experiment, four groups of animals were used consisting of three mice per group. Each group was treated individually: group I treated as negative control, Group II received reference drug of each experiment, Group III and IV received MECV at 200 and 400 mg/kg body weight, respectively. Antidiabetic effect of MECV was evaluated by oral glucose tolerance test. Antidiarrheal activity was examined by the method of castor oil induced diarrhea and reduction in amount of diarrheal feces was determined. To assess the sedative activity of MECV, total sleeping time was determined in phenobarbitone induced mice. Results: MECV showed statistically significant (p<0.05) blood glucose lowering activity which was comparable to the standard drug, glibenclamide and the effect was found to be dose dependent. The extract reduced the diarrheal feces in mice by 51.85% and 65.56% at 200 and 400 mg/kg doses, respectively. The observed activity was found significant (p<0.05) in comparison to the positive control. Also, the test extract showed significant (p<0.05) sedative activity with respect to the control suggesting that the extract potentiated the phenobarbitone induced sleeping time. Conclusion: This is the first report on the therapeutic importance of methanolic extract of Clerodendrum viscosum roots in diabetes, diarrhea and sedation and thus supporting the uses of the plant in traditional medicine.

A review of available herbal medicine options for the treatment of chronic insomnia

Background: Insomnia is a universal health problem that affects the health and quality of life of people worldwide. During the last decade treatment of insomnia with herbal has been introduced to be effective but unfortunately, the safety and efficacy of these medicines are currently uncertain. However, the administration of various herbal medicines for insomnia is increasing mainly due to the diversity of various adverse effects of western medication. Objective: The present study is aimed to investigate available herbal medicine options for the treatment of chronic insomnia. Method: All demanded data were retrieved from electronic databases, Natural Medicines, TCMID, Natural Medicines Comprehensive Database, MedlinePlus, PubMed, EMBASE, and Google Scholar. Among them, randomized clinical trials were chosen precisely to be investigated more for seeking any additional information related to the treatment of chronic insomnia. All related papers in English and Persian languages included in the study criteria. At first, 162 articles were chosen to be investigated, then after screening all articles based on the PRISMA method, 83 qualified articles remained to be investigated carefully. Results: Herbal plants with medical properties as sedative agents are obtaining more and more attention because they contain various types of natural bioactive metabolites with the lowest rate of adverse effects. Moreover, these novel medicines are highly economic, with high efficacy while could be available easily. Conclusion: The data from this study demonstrated that medical plants could yield sedative activity and some of them are effective for insomnia, but we must not forget that further clinical trials are demanded to approve this. Keywords: Sleep disorders, Chronic insomnia, Herbal medicine, Alternative medication, Treatment.

Individual and Combined Inhalational Sedative Effects in Mice of Low Molecular Weight Aromatic Compounds Found in Agarwood Aroma

Agarwood is known to have a sedative effect and the less studied volatile aromatic constituents it contains may have contribution to the activity. In this study, two Kyara grade (highest-grade agarwood in Japan) samples were extracted using headspace-solid phase microextraction (HS-SPME) and analyzed through gas chromatography-mass spectrometry (GC-MS). Six low molecular weight aromatic compounds (LACs) and one structurally simple compound (diethylene glycol monoethyl ether) present in the aromas were individually evaluated for inhalational sedative activity in mice through open field test. Doses of 0.0001 g/L to 1 g/L were prepared for each compound and administered to mice (n = 6/dose/compound). Results revealed all compounds decreased spontaneous motor activity at almost all doses. Strongest sedative activity of each compound reduced total spontaneous motor activity by more than half against control, demonstrating their contribution to agarwood aroma and potential as independent sedating agents. Mixtures of compounds using their most effective dose were made and evaluated again for inhalational sedative effect. Interestingly, the combination of all compounds showed no significant effect and even caused stimulation in mice movements. This result suggests antagonistic-like interaction between the compounds, which is probably due to structural similarities. Consequently, it implies the other constituents present in agarwood, along with LACs, are also important to the overall sedative activity.

Bioresearch of New 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones

The subject of the work was the synthesis of new derivatives of1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione with potential analgesic and sedative activity. Eight compounds werereceived. The analgesic activity of the new compounds was confirmed in the “hot plate” test and in the “writhing” test. All tested imides 8–15 were more active in the “writhing” test than aspirin, and two of them, 9 and 11, were similar to morphine. In addition, all of the new imides inhibited the locomotor activity in mice to a statistically significant extent, and two of them also prolonged the duration of thiopental sleep.On the basis of the results obtained for the previously synthesized imides and the results presented in this paper, an attempt was madeto determine the relationship between thechemical structure of imides and their analgesic and sedativeproperties.

Phytochemical and Pharmacological Investigations of Lannea grandis (Dennst.) Engl. Leaves Extracts

Medicinal plants can serve as a prominent source of bioactive secondary metabolites which can exert beneficial effects to combat against many human diseases. Lannea grandis (Dennst.) Engl, a member of Anacardiaceae family has several applications in the ethnomedical practices. In this study, the ethanol extract of L. grandis leaf (ELG) along with its petroleum-ether and chloroform fractions were subjected to phytochemical analysis along with the evaluation of antimicrobial, anti-diarrheal, and sedative activities using standard protocols. Phytochemical screening was performed according to common phytochemical tests. Antimicrobial assay was carried out by disc diffusion method where the ethanol extract of L. grandis showed significant activity against tested bacterial species (zone of inhibitions = 10.8±0.85 to 13.8±1.84 mm). The same extract also exhibited the highest antifungal activity against Blastomyces dermatitidis (zone of inhibition = 20.5±0.35 mm). The chloroform fraction of L. grandis at the dose of 400 mg/kg body weight produced a significant (p<0.05) anti-diarrheal effect with 40.69% inhibition of castor oil-induced diarrhea in mice. During sedative activity assay in mice, the plant extract at the dose of 400 mg/kg body weight produced mild reduction in the time of onset of sleep and increased the length of the sleeping time induced by a sedative, phenobarbitone. In conclusion, the plant L. grandis can be considered as a base for the development of new drugs and phytomedicine. Keywords: Lannea grandis, phytochemical, antimicrobial, anti-diarrheal, sedative activity.