Bioguided Isolation of Alkaloids and Pharmacological Effects of the Total Alkaloid Fraction from Aspidosperma pyrifolium Mart. (Apocynaceae)

Aspidosperma pyrifolium is used in traditional medicine to treat inflammatory disorders. The aim of the study was to perform phytochemical characterization and evaluate the anti-inflammatory, anti-nociceptive and acute toxicity effects of the total alkaloid fraction (TAF-Ap) from stem barks. Two monoterpenic indole alkaloids were isolated by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) and the structural elucidation was performed using 1D and 2D NMR analysis. As for toxicity, no animals died at 50 mg kg−1 and this concentration presented mild sedation and forced breathing within the first 24 h. The lethal dose capable of killing 50% of the animals (LD50) was estimated to be 160 mg kg−1. In the pharmacological tests, the models used were 1% carrageenan-induced paw edema and peritonitis, 1% formalin-induced nociception and 1% acetic acid-induced abdominal writhing in Swiss mice. The study made it possible to isolate 15-methoxyaspidospermine and 15-methoxypyrifolidine, corroborating the results of pharmacological assays, which showed anti-inflammatory and analgesic potential, especially at 30 mg kg−1 (p < 0.001). Thus, the species was shown to be a promising source of active substances, with special attention paid to its toxicological potential.

Assessment of the Total Flavonoid, Phenol, Alkaloid Content and Sun Protection Factor in Grewia abutilifolia Leaf Extract

A variety of secondary metabolites provide a valuable source of treatment for various pharmacological ailments. Grewia abutilifolia is a shrub found in the family Tiliaceae that is also investigated for its nutritional and medicinal benefits. Grewia is reported for its good antioxidant potential, which is applied to protect skin from UV rays. The main goal of this study is to determine the in-vitro sunscreen effect of Grewia abutilifolia based on phytochemical evidence of UV protection. Chemical treatments used to protect skin from the sun have several drawbacks, including numerous hazardous side effects on humans and the environment. The hydroalcoholic, ethyl acetate, and methanolic extracts were studied for their phytochemical, physicochemical, and sun protection activities. Total phenolic content, total alkaloid content, total flavonoid content, and SPF value were all highest in the methanolic leaf extract, with values of 99.20 0.12, 47.661.527, 96.02, and 14.50.01 for total phenolic content, total alkaloid content, total flavonoid content, and SPF value, respectively.

The Cultivation of Chelidonium majus L. Increased the Total Alkaloid Content and Cytotoxic Activity Compared with Those of Wild-Grown Plants

The effect of cultivation practises on both the phytochemical profile and biological activity of aqueous ethanol extracts of Chelidonium majus L. was studied. Extracts were prepared from aerial parts of the same plant population collected in the wild and grown under organic farming conditions. Both qualitative and quantitative analyses of alkaloids and flavonoid derivatives were performed by LC/MS methods, and the cytotoxicity of lyophilised extracts was studied in B16-F10, HepG2, and CaCo-2 cells. Coptisine was the dominant alkaloid of extracts prepared from wild-grown plants, whereas after cultivation, chelidonine was the most abundant alkaloid. The total alkaloid content was significantly increased by cultivation. Ten flavonol glycoconjugates were identified in C. majus extracts, and quantitative analysis did not reveal significant differences between extracts prepared from wild-grown and cultivated specimens. Treatment with C. majus extracts resulted in a dose-dependent increase in cytotoxicity in all three cell lines. The extracts prepared from cultivated specimens showed higher cytotoxicity than the extracts prepared from wild-grown plants. The strongest cytotoxic effect of cultivated C. majus was observed in B16-F10 cells (IC50 = 174.98 ± 1.12 µg/mL). Cultivation-induced differences in the phytochemical composition of C. majus extracts resulted in significant increases in the cytotoxic activities of the preparations.

Pharmacokinetic, acute toxicity, and pharmacodynamic studies of semen strychni total alkaloid microcapsules

Purpose: To investigate the safety and effectiveness of semen strychni total alkaloid microcapsules (SSTAM), compared with semen strychni total alkaloids (SSTA). Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to assess pharmacokinetics of brucine and strychnine in rats. Acute toxicity was investigated in pre-test and formal experiments in mice. The pharmacodynamics of SSTAM and SSTA were evaluated by their analgesic and anti-inflammatory activities. Results: With respect to brucine, the half-life of SSTA group (1.6 mg/kg), low-dose SSTAM group (6 mg/kg) and high-dose SSTAM group (10 mg/kg) was 5.723, 9.321 and 9.025 h, respectively. With respect to strychnine, the half-life of SSTA group, low-dose SSTAM group and high-dose SSTAM group was 4.065, 8.819 and 8.654 h, respectively. The LD50 values of SSTAM group and SSTA group were 236.59 and 30.27 mg/kg, respectively. The pain inhibition rates of SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group (p < 0.05) while the pain threshold values of the SSTAM groups (25 and 50 mg/kg) were higher than that of blank control (p < 0.01) and SSTA groups (p < 0.01) at 60 min and 120 min. The inhibition rates of the SSTAM groups (25 and 50 mg/kg) were higher than that of SSTA group based on ear swelling and cotton ball granulation tests. Compared with blank control and SSTA groups, the absorbance values of SSTAM groups (25 and 50 mg/kg) were lower (p < 0.01). Conclusion: SSTAM increases the dosage of administration but reducea the toxicity of the alkaloids in rats, and is thus a potentially safe and effective drug delivery system.

Alkaloid Cytotoxic Test on Ethanol Extract from Itchy Leaves (Laportea decumana (Roxb.) Wedd.)

The Itchy leaf [Laportea decumana (Roxb.) Wedd] is a plant that is widely used as traditional medicine by Papuans as a pain reliever. The purpose of this study was to determine the total level of alkaloids in itchy leaf extract and to test the cytotoxic activity using the BSLT method. The research series began with the extraction stage with the maceration method using 96% ethanol, which tested the alkaloid level. The test was carried out using the gravimetric method and the cytotoxic test using the alkaloid level test results using the BSLT method on shrimp larvae (Artemia salina L). The results showed that itchy leaf extract contained a total alkaloid level of 6.46%. Cytotoxic testing using the BSLT method showed an LC50 of 54.33 ppm and was found to be toxic.

Improving large-scale biomass and total alkaloid production of Dendrobium nobile Lindl. using a temporary immersion system and MeJA

Background Dendrobium nobile Lindl. is an important pharmacopeial plant with medicinal and ornamental value. This study sought to provide technical means for the large-scale artificial production of total alkaloids in D. nobile. Seedlings were cultured in vitro in a temporary immersion bioreactor system (TIBS). The four tested immersion frequencies (min/h; 5/2, 5/4, 5/6, and 5/8) influenced the production of biomass and total alkaloid content. In addition, to compare the effects of different concentrations of phytohormone methyl jasmonate (MeJA) and treatment time on biomass and total alkaloid accumulation, MeJA was added to the TIBS medium after 50 days. Finally, the production of total alkaloids in a semi-solid system (SSS), TIBS, and TIBS combined with the MeJA system (TIBS-MeJA) were compared. Results The best immersion frequency was found to be 5/6 (5 min every 6 h) that ensured good levels of biomass and total alkaloid content in plantlets. 10 µM MeJA and 20 days of culture were the most favorable for alkaloid accumulation in the seedlings cultured in TIBS. The maximum content and productivity of total alkaloid on use of TIBS-MeJA was 2.32- and 4.69- fold, respectively, higher in terms of content, and 2.04- and 10.27- fold, respectively, higher in terms of productivity than those on use of TIBS and SSS. Conclusions Our results show that TIBS-MeJA is suitable for the large-scale production of total alkaloids in in vitro seedlings; therefore, they provide technical means for the large-scale artificial production of total alkaloids in D. nobile.

Application of Ultrasonic-Assisted Fractionation with Full-Factorial Design for the Production of Alkaloid-Rich Fraction from Ficus septica Leaves

Ficus septica Burm. F (Awar-awar) in Indonesian herbal medicine traditionally used for the treatment of various disease. Previous studies indicated that the F. septica leaves contained phenantroindolizidine alkaloids with anticancer activity. Fractionation of the ethanol extract of F. septica leaves using n-hexane was able to separate chlorophylls and other inert non–polar constituents from the extract. This fractionation process can be optimized using ultrasonic-assisted fractionation to yield n-hexane insoluble fraction (HIF) that is rich in alkaloids. This study aimed to produce HIF from the ethanol extract of F. septica leaves by using optimized ultrasonic-assisted fractionation with n-hexane as a solvent and full factorial as experimental design. Ficus septica leaves were macerated in ethanol (60%) and the extract was used for the ultrasonic-assisted fractionation process. The duration of fractionation (5-30 minutes), the extract : n-hexane ratios (1:0.1 - 1:1.66 ml/ml), and the ultrasonic power (21-106 Wrms) were optimized to determine the optimal condition for each variable. These optimal variables were used for the production of HIF from the extract by using full factorial design in the ultrasonic-assisted fractionation process. The total alkaloid content was measured using spectrophotometry and was used as parameter for the optimization process. We found that the optimal condition for the fractionation process based on each single variable optimization were 5 minutes of the fractionation duration, 66-70Wrms of the ultrasonic power, and 1:0.7 - 1:0.8 of the extract : n-hexane ratio. By using these optimized variables, the ultrasonic-assisted fractionation using full factorial design yielded up to 0.035% total alkaloid content which is almost double from those in the extract (0.019%). This study provided a basic experimental model for the production of alkaloid-enriched HIF from F. septica leaves in the industrial or pilot scale, and might contribute to the development of Indonesian herbal medicine products from natural resources.