TL;DR: The results suggest that NJM/fractions possess significant antiproliferative potential which is mediated through cell cycle perturbation and pro-apoptotic effects in MDA-MB-231 cells, and highlights the antioxidant potential of NJM-fractions which can be attributed to the presence of phenols.
Abstract: Nardostachys jatamansi DC is a Himalayan medicinal herb that has been described in various traditional systems of medicine for its use in cancer. In view of its traditional claims, and chemical constituents, antioxidant and anticancer activities were evaluated in breast carcinoma. Petroleum ether (NJPE), methanol extract (NJM) and subsequent diethyl ether (NJDE), ethyl acetate (NJEA) and aqueous (NJAQ) fractions of roots and rhizomes of N. jatamansi were prepared. Total phenolic, flavonoid content, and antioxidant activities were determined using suitable methods. Antiproliferative activity was assessed in estrogen receptor (ER)-positive (MCF-7) and ER-negative breast carcinoma (MDA-MB-231) cells by MTT and SRB assay. Cell cycle analysis, Hoechst staining, and clonogenic assay were employed to determine the mode of antiproliferative and pro-apoptotic activity in MDA-MB-231 cells. NJM/fractions exhibited prominent antioxidant activity with significant correlation between phenolic content and ABTS (IC50) scavenging (R = −0.9680, P 0.05). In MTT assay, NJM exhibited the highest antiproliferative activity (IC50: 58.01 ± 6.13 and 23.83 ± 0.69 μg/mL in MCF-7 and MDA-MB-231 respectively). Among the fractions, NJPE and NJDE were found to be most potent in MCF-7 (IC50: 60.59 ± 4.78 μg/mL) and MDA-MB-231 (IC50: 25.04 ± 0.90 μg/mL) cells respectively. Statistical analyses revealed NJM and NJDE exhibited significantly higher (P < 0.05) cytotoxicity in MDA-MB-231 cells. Cell cycle analysis demonstrated that NJM, NJPE and NJEA caused G2/M arrest while NJDE caused G0/G1 phase arrest in MDA-MB-231 cells. Further, NJM/fractions induced significant (P < 0.001) cell death by apoptosis characterized by apoptotic morphological changes in Hoechst staining and inhibited long-term proliferation (P < 0.001) of MDA-MB-231 cells in clonogenic assay. Lupeol and β-sitosterol were identified as anticancer principles in NJM/fractions by HPTLC. Our results suggest that NJM/fractions possess significant antiproliferative potential which is mediated through cell cycle perturbation and pro-apoptotic effects in MDA-MB-231 cells. Moreover, this study highlights the antioxidant potential of NJM/fractions which can be attributed to the presence of phenols. NJDE emerged as the most potent fraction and further mechanistic and phytochemical investigations are under way to identify the active principles.
TL;DR: In toxicological studies on rats and mice an oral LD50 of greater than 3160 mg/kg was found, which suggests the possibility of a therapeutically useful dose ratio.
Abstract: The known sesquiterpene valeranone (= Yatamanson) was isolated from the subterranian parts of Nardostachys yatamansi (DC). It was pharmacologically investigated in animal experiments of sedative, tranquilizing and antihypertensive properties. In some experiments, typical for tranquilizers, certain activities could be demonstrated such as the prolongation of barbiturate hypnosis, the impairment of rotarod performance, an anticonvulsive activity on electric shock and potentiation of the body-temperature lowering activity of reserpine. In three other pharmacological models an anti-ulcer action was detected. In general the activity of valeranone was lower than those of the standard substances used. As regards the hypotensive property only a weak activity was demonstrated. In toxicological studies on rats and mice an oral LD50 of greater than 3160 mg/kg was found, which suggests the possibility of a therapeutically useful dose ratio.
TL;DR: Three new diterpene compounds and a new monoterpene, 6-hydroxy-7-(hydroxymethyl)-4-methylenehexahydrocyclopenta[c]pyran-1(3H)-one, together with four known sesquiterpenes, delta1(10)-aristolene-9beta-ol, debilon, nardosinone, and kanshone A, were isolated from the roots of N
Abstract: A new diterpene, 10-isopropyl-2,2,6-trimethyl-2,3,4,5-tetrahydronaphtha[1,8-bc]oxocine-5,11-diol (1), and a new monoterpene, 6-hydroxy-7-(hydroxymethyl)-4-methylenehexahydrocyclopenta[c]pyran-1(3H)-one, together with four known sesquiterpenes, delta1(10)-aristolene-9beta-ol, debilon, nardosinone, and kanshone A, were isolated from the roots of Nardostachys chinensis. The structures of the new compounds were established on the basis of their spectroscopic data, and the structure of 1 was confirmed by X-ray crystallographic analysis.
TL;DR: Eleven compounds could be potential natural product scaffolds for developing drug candidates targeting SERT, among which, kanshone C of aristolane-type sesquiterpenoid inhibited SERT most strongly, while desoxo-nachinol A of nardosinane- type sesQUiterpenoids instead enhanced SERT potently.
Abstract: Serotonin transporter (SERT) is a classic target of drug discovery for neuropsychiatric and digestive disorders, and against those disorders, plants of Nardostachys genus have been valued for centuries in the systems of Traditional Chinese Medicine, Ayurvedic and Unani. Herein, chemical investigation on the roots and rhizomes of Nardostachys chinensis Batal. led to the isolation of forty sesquiterpenoids including six new aristolane-type sesquiterpenoids and six new nardosinane-type sesquiterprenoids. Their structures were elucidated by extensive spectroscopic methods, combined with analyses of circular dichroism and single-crystal X-ray diffraction data. To explore natural product scaffolds with SERT regulating activity, a high-content assay for measurement of SERT function in vitro was conducted to evaluate the SERT regulating properties of these isolates. In conclusion, eleven compounds could be potential natural product scaffolds for developing drug candidates targeting SERT. Among which, kanshone C of aristolane-type sesquiterpenoid inhibited SERT most strongly, while desoxo-nachinol A of nardosinane-type sesquiterpenoid instead enhanced SERT potently.
TL;DR: Results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression.
Abstract: AIM: To determine if the fraction of Nardostachys jatamansi (NJ) has the potential to ameliorate the severity of acute pancreatitis (AP).
METHODS: Mice were administered the biologically active fraction of NJ, i.e., the 4th fraction (NJ4), intraperitoneally, and then injected with the stable cholecystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination, measurement of cytokine expression, and examination of neutrophil infiltration.
RESULTS: NJ4 administration attenuated the severity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heme oxygenase-1 (HO-1). Furthermore, NJ4 and its biologically active fraction, NJ4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pancreatic acinar cells.
CONCLUSION: These results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression.