Role of Chitosan-Loaded Solanine Glycoalkaloid from Solanum scabrum Mill. Leaf Extract as Anti-Inflammatory and In Vitro Anticancer Agents.

Objectives: Solanum scabrum Mill. commonly "African nightshade" or "huckleberry" is a plant, whose leaves are used by tribes in Nigeria and Cameroon for making the popular "Kombi" and "Njama Njama" soups, respectively. This study aimed to evaluate the anti-inflammatory and anticancer activities of the leaf crude methanol extract from S. scabrum. Materials and Methods: Fractions of the plant were tested for anti-inflammatory potential and in vitro anticancer activity on MCF-7 and HMVII cell lines by carrageenan-induced oedema in mice, and cytotoxicity assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, transwell migration and invasion assays, and apoptosis study by flow cytometry, respectively. Results: Bioguided isolation yielded a white crystalline compound 3-nitro dibenzofuran (C12H7NO3, m/z; 213.19 g/mol, m.p.; 181.49 °C). 1H-NMR showed seven signals at δ (ppm) 2.8-4.3 consisting of two doublets and five singlets, while 13C-NMR revealed twelve carbons, which are majorly methyl carbons at δ (ppm) between 120 and 195. All tested samples demonstrated dose-dependent anti-inflammatory activity in carrageenan-induced mice. The isolated compound, i.e. solanine, and chitosan-loaded drugs showed significant inhibitory activity on the cell lines with inhibitory concentration 50 (IC50) values of 8.52, 0.82, and 22.1 µg/mL, respectively on MCF-7 cell line and 4.54, 0.08, and 12.1 µg/mL, respectively, on HMVII cell line, while doxorubicin (adriamycin) positive control, had IC50 values of 0.02 and 0.06 µg/mL, respectively, on MCF-7 and HMVII cancer cells. Selectivity index of solanine was the lowest in the study, hence, it lacks the ability to differentiate between cancerous and normal cell Vero E6 cell lines. Chitosan-loaded drugs quicken early apoptosis and sustained late apoptosis in cells with much improved selective indices. Conclusion: The results obtained from this study further affirmed the use of chitosan nanoparticles as carriers for anticancer drugs.

Pharmacognostic profiles, evaluation of analgesic, anti-inflammatory and anticonvulsant activities of Newbouldia laevis (P. Beauv.) Seem. ex Bureau leaf and root extracts in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Newbouldia laevis is a popular medicinal plant whose leaves and roots are used in Nigeria as ethnomedicinal prescriptions for pain, inflammation, convulsion, and epilepsy. These claims have not been scientifically verified prior to this study. AIM OF THE STUDY: To determine pharmacognostic profiles of the leaves and roots and evaluate the analgesic, anti-inflammatory, and anticonvulsant activities of methanol leaf and root extracts in Wistar rats. MATERIAL AND METHODS: The pharmacognostic profiles of the leaves and roots were determined using standard procedures to serve as fingerprints for the plant. The methanol leaf and root extracts of Newbouldia laevis were tested for acute toxicity using the OECD's up and down method at the maximum dose of 2000 mg/kg (orally) in Wistar rats. Analgesic studies were carried out in acetic acid-induced writhing in rats and tail immersion. The anti-inflammatory activity of the extracts was evaluated using carrageenan-induced rat paw-oedema and formalin-induced inflammation in rats' mode. The anticonvulsant activity was determined using strychnine-induced, pentylenetetrazol-induced, and maximal electroshock-induced rat convulsion models. For each of these studies, the extracts doses of 100, 200 and 400 mg/kg were administered to the rats following the oral route. RESULTS: The pharmacognostic profiles showed that the leaves possessed deep-sunken paracytic stomata (5-8-16 mm2; adaxial, 8-11-24 mm2; abaxial epidermis), vein islets (2-4-10 mm2; adaxial), vein terminations (10-14-18 mm2; adaxial), palisade ratio (8.3-12.5-16.4 mm2; adaxial, 2.5-6.8-12.2 mm2; adaxial), covering unicellular trichome (8-14; adaxial), spheroidal calcium oxalate crystals (3-5 µm), and oval-shaped striated starch grain with no hilum (0.5-4.3 µm). The transverse section of the leaf showed the presence of spongy and palisade parenchyma as well as a closed vascular bundle. The root powder showed the presence of brachy sclereid, fibers without lumen, and lignin. All physicochemical parameters fall within the acceptable limits, phytochemical contents showed mainly glycosides, alkaloids, and steroids while acute oral toxicity (LD50) of the parts for 14 days did not produce any toxicity signs or mortality in the rats. The extracts produced dose-dependent (100-400 mg/kg) analgesic involving opioid receptors, anti-inflammatory, and anticonvulsant activities in the rats which were significant (p ≤ 0.05) when compared to the standard drugs. The leaf extract possessed the most potent analgesic and anti-inflammatory effects in the rats, while the most anticonvulsant effects were observed in rats treated with the leaf extract. Both extracts showed elevated levels of protection against strychnine-induced, pentylenetetrazol-induced, and maximal electroshock-induced seizure in rats. CONCLUSION: Our study revealed some pharmacognostic profiles of Newbouldia laevis leaves and roots that are vital for its identification from closely related species often used for adulteration in traditional medicine. The study further showed that the leaf and root extracts of the plant possessed dose-dependent analgesics, anti-inflammatory and anti-convulsant activities in rats, thus, justifying its use for the treatment of these diseases in Nigerian traditional medicine. There is a need to further study its mechanisms of action towards drug discovery.

Evaluation of physicochemical parameters, acute and subchronic toxicities, and anti-diabetic activity of Spondias venulosa (Engl.) Mart. ex Engl. leaf extract on alloxan-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Spondias venulosa is a medicinal plant whose leaves are popularly used for decades in Northeast Nigeria as a first-choice medicinal plants for the treatment of diabetes. This claim has not been proven scientifically. AIM OF THE STUDY: The present study was carried out to determine the physicochemical profiles, acute, sub-chronic toxicities, and antidiabetic activity the leaf extract in alloxan-induced diabetic rats. MATERIALS AND METHODS: The physicochemical parameters of S. venulosa leaves, acute, subchronic toxicities, and antidiabetic activity in alloxan-induced diabetic rats were determined using standard procedures. All physicochemical parameters were carried out triplicate. Acute and subchronic toxicity studies were carried out following OECD guidelines by administering maximum extract dose of 2000 mg/kg orally to Wistar rats. Subchronic toxicity and antidiabetic studies were carried out in rats of opposite sexes at doses 300, 600, and 1200 mg/kg (orally). RESULTS: Results obtained showed that the moisture content, water soluble extractive, and organic matter had values of 4.98 ± 1.01, 12.04 ± 1.24 and 1.01 ± 0.01% w/w respectively. The metallic contents of the methanol leaf extract revealed the presence of zinc with value of 12.01 ± 1.01 ppm (normal range:< 100 mg/kg DM) and copper with value of 6.24 ± 2.14 ppm (normal range:< 30 mg/kg DM). Oral median lethal dose (LD50) was estimated to be greater than 2000 mg/kg since the extract did not produce any sign of toxicity or death in short term while, subchronic toxicity study showed that there was no significant weight loss in the rats after 28 days of extract administration. All hematology and biochemical parameters showed no elevated values when compared to the control group (p < 0.05). Histopathological examinations of major organs do not show signs of organ damages which indicate that the extract was safe at the doses administered. Oral administration of extract doses for 30 days reduced blood glucose levels in alloxan-induced diabetic rats in dose-dependent manner compared (p < 0.05) to standard drug (Glibenclamide). CONCLUSIONS: Our study showed some physicochemical parameters of S. venulosa leaf which are essential for its identification from closely related species in traditional medicine. The study further showed that S. venulosa methanol leaf extract possessed antidiabetic activity, thus, justifying its use for the treatment of diabetes in Nigeria. However, there is need to identify and investigate the bioactive compound(s) responsible for the activity towards drug discovery.