Achyut Adhikari

Iridoid Glycoside from the Leaves of Clerodendrum volubile Beauv. Shows Potent Antioxidant Activity Against Oxidative Stress in Rat Brain and Hepatic Tissues

ABSTRACT Aim: This study aims at reporting the isolation, structure elucidation, and antioxidant potentials of ajugoside from C. volubile leaves in sodium nitroprusside (SNP)-induced oxidative stressed rat brain and hepatic tissues. Materials and Method: An iridoid monoterpene, ajugoside was isolated from the n-butanol fraction of C. volubile and evaluated for its antioxidant protective potential on brain and liver tissues of male Wister rats in an ex vivo model. Two molar concentrations (6.4 × 10−4 M and 1.28 × 10−3 M) of the metabolite and SNP were incubated with the tissues homogenate at 37°C for 2 hr prior to the test and assayed for catalase, superoxide dismutase (SOD) activities, and lipid peroxidation. α tocopherol (6.4 × 10−4 M) was used as standard. Results: Both molar concentrations exhibited high catalase activity in the tissues. However, 6.4 × 10−4 M ajugoside exhibited a very high SOD activity (liver: 96.45 and brain: 96.30%) and inhibition of lipid peroxidation (liver: 88.11 and brain: 93.27%) compared to the standard. 1.28 × 10−3 M ajugoside also exhibited good activities but lower than that of the standard and 6.4 × 10−4 M ajugoside. Discussion and Conclusion: Ajugoside showed potent antioxidant activities as evidenced by the synergistic high activities of SOD and catalase as well as inhibition of lipid peroxidation in the studied tissues.

Leishmanicidal Evaluation of Tetrahydroprotoberberine and Spirocyclic Erythrina-Alkaloids

Leishmaniasis is one of the World’s most problematic diseases in developing countries. Traditional medicines to treat leishmaniasis have serious side effects, as well as significant parasite resistance problems. In this work, two alkaloids 1 and 2 were obtained from Corydalis govaniana Wall and seven alkaloids 3–9, were obtained from Erythrina verna. The structures of the compounds were confirmed by mass spectrometry and 1D- and 2D-NMR spectroscopy. The leishmanicidal activity of compounds 1–9 against Leishmania amazonensis was tested on promastigote forms and cytotoxicity against J774 (macrophage cell line) was assessed in vitro. Compound 1 showed potent activity (IC50 = 0.18 µg/mL), compared with the standard amphotericin B (IC50 = 0.20 µg/mL). The spirocyclic erythrina-alkaloids showed lower leishmanicidal activity than dibenzoquinolizine type alkaloids.

Diterpenoids Including a Novel Dimeric Conjugate from Salvia leriaefolia

Salvialeriafone (1), a novel diterpene-norditerpene conjugate, was isolated from Salvia leriaefolia. Additionally, two new abietane-type diterpenoids, salvialerial (2) and salvialerione (3), as well as four known compounds, sugiol (4), salvicanaric acid (5), dehydroroyleanone (6), and cariocal (7), were isolated and identified. Their structures were determined by spectroscopic data analyses. Known compounds were isolated from this plant for the first time. Compounds 1, 5, 6, and 7 exhibited IN VITRO antiproliferative activity against the human cervical cancer cell line (Hela), while 6 showed cytotoxicity against the human prostate cancer cell line (PC3).

Govanoside A, a new steroidal saponin from rhizomes of Trillium govanianum.

A new spirostane steroidal saponin, govanoside A (1) along with three known compounds borassoside E (2) pennogenin (3) and diosgenin (4) were isolated from rhizomes of Trillium govanianum. Their structures were elucidated through 1D, 2D-NMR spectroscopic data analysis and acid hydrolysis. Compound (2) in genus Trillium and all compounds (1-4) in T. govanianum are reported herein for the first time. Furthermore, compounds 1 &2 exhibited good to moderate activities against Aspergillus niger ATCC 16888, Aspergillus flavus ATCC 9643, Candida albicans ATCC 18804, and Candida glabrata ATCC 90030. This is a significant finding keeping in view the limited antifungal drugs for aspergillosis and candidiasis.

First evidence of the analgesic activity of govaniadine, an alkaloid isolated from Corydalis govaniana Wall.

In this work, govaniadine, an alkaloid isolated from Corydalis govaniana Wall. was evaluated for its analgesic activity by writhing and hot-plate tests. Govaniadine did not display any toxic effects in mice up to 20 mg/kg during 24 h assessment study. The acetic acid-induced writhing was significantly reduced by pretreatment with govaniadine in a dose-dependent manner (1.25–5.0 mg/kg, intraperitoneally (i.p.)). Furthermore, molecular docking study has shown that this alkaloid binds the COX-2 enzyme. In the hot-plate test, govaniadine at dose of 2.5 and 5 mg/kg, i.p. displayed analgesic effect at all time points (30, 60, 90 and 120 min). The analgesic effect of govaniadine was significantly antagonised by naloxone administration. Our results demonstrate for the first time that the peripheral and central analgesic effects of govaniadine could be in part related to the involvement of COX-2 activity and by its interaction with the opioid system.

Molecular simulations probing Kushecarpin A as a new lipoxygenase inhibitor

Zizyphus oxyphylla Edgew is used in Pakistan as a folk medicinal remedy for inflammatory conditions, pains especially rheumatic pain, fevers, allergy and diabetes. The aim of the current study was to scientifically validate the folk use of Z. oxyphylla Edgew by using the isolated compound in vitro and in vivo levels. Kushecarpin A was isolated from ethyl acetate fraction of the plant crude extract. Molecular docking simulations predicted Kushecarpin A as a potential new lipoxygenase (LOX) inhibitor. Kushecarpin A showed significant lipoxygenase inhibition (IC(50): 7.2 ± 0.02 μM) thus validated computational prediction. It also exhibited significant and highly significant inhibition (p < 0.05 and p < 0.01) of carrageenan-induced hind paw oedema at the doses of 5, 10 and 20 mg/kg. Kushecarpin A seems to be a potentially new anti-inflammatory compound responsible for anti-inflammatory activities of Z. oxyphylla Edgew. In vitro and in vivo anti-inflammatory inflammatory activities were found in good agreement with the folk medicinal use of Z. oxyphylla Edgew in inflammatory disorders.

Anti-inflammatory and enzyme inhibitory activities of a crude extract and a pterocarpan isolated from the aerial parts of Vitex agnus-castus.

A new compound, 6a,11a-dihydro-6H-[1] benzofuro [3,2-c][1,3]dioxolo[4,5-g]chromen-9-ol was isolated from the ethyl acetate fraction of Vitex agnus-castus. The structure of this compound was identified with the help of spectroscopic techniques ((13)C NMR, (1)H NMR, HMBC, HMQC, NOESY and COSY). The compound showed low urease- (32.0%) and chymotrypsin- (31.4%) inhibitory activity, and moderate (41.3%) anti-inflammatory activity. The crude extract and various fractions obtained from the aerial parts of the plant were also screened for possible in vitro hemagglutination, antibacterial and phytotoxic activities. No hemagglutination activity against human erythrocytes was observed in crude extracts and fractions of V. agnus-castus. The fractions and crude methanolic extract showed moderate and low antibacterial activity. Exceptions were the CHCl(3) fraction, which showed significant antibacterial activity against Klebsiella pneumonia (81% with MIC(50)=2.19 mg/mL), the n-hexane fraction, which exhibited no activity against Salmonella typhi, and the CHCl(3) and aqueous fractions, which showed no activity against Bacillus pumalis. Moderate phytotoxic activity (62.5%) was observed by n-hexane fraction of V. agnus-castus against Lemna minor L at 1000 μg/mL.

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf

Abstract The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC50 value of 27.10 ± 0.0 μg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC50 = 36.10 ± 3.4 and 56.30 ± 2.1 μg/mL, respectively. Compound 1 was less effective (IC50 > 100 μg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 μM. Graphical abstract

Analgesic and antiinflammatory activities of taxoids from Taxus wallichiana Zucc.

A study was conducted to identify constituents that might be responsible for analgesic and antiinflammatory conditions. Tasumatrol B, 1,13‐diacetyl‐10‐deacetylbaccatin III (10‐DAD) and 4‐deacetylbaccatin III (4‐DAB) were isolated from the bark extract of Taxus wallichiana Zucc. All the compounds were assessed for analgesic and antiinflammatory activities using an acetic acid‐induced writhing model, a hot‐plate test, a carrageenan‐induced paw oedema model, a cotton‐pellet oedema model and in vitro lipoxygenase inhibitory assay. All the compounds, especially tasumatrol B, revealed significant analgesic activity in comparison to a saline group based on an acetic acid‐induced model. Similarly all of the test compounds, particularly tasumatrol B, showed significant antiinflammatory activity. However, all the compounds failed to exhibit any considerable activity in of the hot‐plate test and the in vitro lipoxygenase inhibitory assay. This study has highlighted the potential of tasumatrol B to be further explored as a new lead compound for the management of pain and inflammation, one that has been discovered by scientific validation of the traditional medicinal use of T. wallichiana Zucc. Copyright

Drimane-Type Sesquiterpenes from Polygonum hydropiper

One new drimane-type sesquiterpenoid, 3 β-angeloyloxy-7-epifutronolide (1), and one new natural product, polygonumate (2), along with six known drimane-type sesquiterpenes [dendocarbin L (3), (+) winterin (4), (+) fuegin (5), changweikangic acid A (6), futronolide (7), and 7-ketoisodrimenin (8)] were isolated from the whole plant of Polygonum hydropiper Linn. Their structures were determined using spectroscopic techniques. Single-crystal X-ray diffraction study on dendocarbin L (3) and ¹³C-NMR spectroscopic data of (+) winterin (4) are described for the first time. Compound 6 was evaluated for inhibitions of α-chymotrypsin, acetylcholinesterase, and butyrylcholinesterase enzymes.