(3r)-7,2'-Dihydroxy-3',4'-dimethoxyisoflavan

Inhibition of Osteoarthritis-Related Molecules by Isomucronulatol 7-O-beta-d-glucoside and Ecliptasaponin A in IL-1beta-Stimulated Chondrosarcoma Cell Model.[Pubmed:30380653]

Molecules. 2018 Oct 29;23(11). pii: molecules23112807.

Osteoarthritis (OA) is the common form of arthritis and is characterized by disability and cartilage degradation. Although natural product extracts have been reported to have anti-osteoarthritic effects, the potential bioactivity of Ryupunghwan (RPH), a traditional Korean medicinal botanical formula that contains Astragalus membranaceus, Turnera diffusa, Achyranthes bidentata, Angelica gigas, Eclipta prostrata, Eucommia ulmoides, and Ilex paraguariensis, is not known well. Therefore, the inhibitory effects of single compounds isolated from RPH on the OA-related molecules were investigated using IL-1beta-stimulated chondrosarcoma SW1353 (SW1353) cell model. Two bioactive compounds, isomucronulatol 7-O-beta-d-glucoside (IMG) and ecliptasaponin A (ES) were isolated and purified from RPH using column chromatography, and then the structures were analyzed using ESI-MS, (1)H-NMR, and (13)C-NMR spectrum. The expression or amount of matrix metalloproteinase 13 (MMP13), COX1/2, TNF-alpha, IL-1beta or p65 was determined by RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA). RPH pretreatment reduced the expression and amounts of MMP13, and the expression of collagen II, COX1/2, TNF-alpha, IL-1beta or p65, which were increased in IL-1beta-stimulated SW1353 cells. IMG reduced the expression of all OA-related molecules, but the observed inhibitory effect was less than that of RPH extract. The other single compound ES showed the reduced expression of all OA-related molecules, and the effect was stronger than that in IMG (approximately 100 fold). Combination pretreatment of both single components remarkably reduced the expression of MMP13, compared to each single component. These synergic effects may provide potential molecular modes of action for the anti-osteoarthritic effects of RPH observed in clinical and animal studies.

Nitric oxide inhibitory flavonoids from traditional Chinese medicine formula Baoyuan Decoction.[Pubmed:25889071]

Fitoterapia. 2015 Jun;103:252-9.

Three new flavonoid glycosides, (3R)-(+)-isomucronulatol-2'-O-beta-D-glucopyranoside (1), (3R)-(-)-isomucronulatol-7-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyranoside (2), and (2S)-(-)-7,8-dihydroxylflavanone-4'-O-beta-D-apiofuranosyl(1-->2)-beta-D-glucopyr anoside (3), along with eight flavanones (4, 8, 10, 12, 15, 16, 21, and 24), four isoflavones (5, 11, 13, and 23), four chalcones (6, 14, 17, and 18), two isoflavans (19-20), one flavone (7), one flavonol (9), and one dihydrochalcone (22) were isolated from Baoyuan Decoction (BYD), a traditional Chinese medicine formula. The structures of the new compounds were established by detailed analysis of NMR and HRESIMS spectroscopic data, and their absolute configurations were determined by electronic circular dichroism (ECD) data. The inhibitory effects of the isolates were evaluated on nitric oxide production in lipopolysaccharide activated RAW 264.7 macrophage cells. Compounds 6, 9, and 10 showed the significant inhibitory activities, with IC50 values of 1.4, 13.8, and 9.3 muM, respectively, comparable to or even better than the positive control, quercetin (IC50, 16.5 muM). The assignment of these isolated flavonoids was achieved using UPLC-Q-trap-MS, and the results suggested that they were originated from Astragalus membranaceus and Glycyrrhiza uralensis.

Bioactive components on immuno-enhancement effects in the traditional Chinese medicine Shenqi Fuzheng Injection based on relevance analysis between chemical HPLC fingerprints and in vivo biological effects.[Pubmed:24950446]

J Ethnopharmacol. 2014 Aug 8;155(1):405-15.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi Fuzheng Injection (SFI) is an injectable traditional Chinese herbal formula comprised of two Chinese herbs, Radix codonopsis and Radix astragali, which were commonly used to improve immune functions against chronic diseases in an integrative and holistic way in China and other East Asian countries for thousands of years. MATERIALS AND METHODS: This present study was designed to explore the bioactive components on immuno-enhancement effects in SFI using the relevance analysis between chemical fingerprints and biological effects in vivo. According to a four-factor, nine-level uniform design, SFI samples were prepared with different proportions of the four portions separated from SFI via high speed counter current chromatography (HSCCC). SFI samples were assessed with high performance liquid chromatography (HPLC) for 23 identified components. For the immunosuppressed murine experiments, biological effects in vivo were evaluated on spleen index (E1), peripheral white blood cell counts (E2), bone marrow cell counts (E3), splenic lymphocyte proliferation (E4), splenic natural killer cell activity (E5), peritoneal macrophage phagocytosis (E6) and the amount of interleukin-2 (E7). Based on the hypothesis that biological effects in vivo varied with differences in components, multivariate relevance analysis, including gray relational analysis (GRA), multi-linear regression analysis (MLRA) and principal component analysis (PCA), were performed to evaluate the contribution of each identified component. RESULTS: The results indicated that the bioactive components of SFI on immuno-enhancement activities were calycosin-7-O-beta-d-glucopyranoside (P9), isomucronulatol-7,2'-di-O-glucoside (P11), biochanin-7-glucoside (P12), 9,10-dimethoxypterocarpan-3-O-xylosylglucoside (P15) and astragaloside IV (P20), which might have positive effects on spleen index (E1), splenic lymphocyte proliferation (E4), splenic natural killer cell activity (E5), peritoneal macrophage phagocytosis (E6) and the amount of interleukin-2 (E7), while 5-hydroxymethyl-furaldehyde (P5) and lobetyolin (P13) might have negative effects on E1, E4, E5, E6 and E7. Finally, the bioactive HPLC fingerprint of SFI based on its bioactive components on immuno-enhancement effects was established for quality control of SFI. CONCLUSIONS: In summary, this study provided a perspective to explore the bioactive components in a traditional Chinese herbal formula with a series of HPLC and animal experiments, which would be helpful to improve quality control and inspire further clinical studies of traditional Chinese medicines.

Flavonoids from Astragalus membranaceus and their inhibitory effects on LPS-stimulated pro-inflammatory cytokine production in bone marrow-derived dendritic cells.[Pubmed:23771500]

Arch Pharm Res. 2014 Feb;37(2):186-92.

Radix Astragali (Astragalus membranaceus) is an important traditional Chinese medicine that is widely used as a tonic to enhance the body's natural defense mechanisms. In this phytochemical study, 12 flavonoids, isoliquiritigenin (1), liquiritigenin (2), calycosin (3), calycosin 7-O-beta-D-glucoside (4), formononetin (5), formononetin 7-O-beta-D-glucoside (6), daidzein (7), daidzein 7-O-beta-D-glucoside (8), methylnissolin (9), methylnissolin 3-O-beta-D-glucoside (10), isomucronulatol (11), and isomucronulatol 7-O-beta-D-glucoside (12), were isolated from the roots of A. membranaceus. Their structures were elucidated by comparing spectroscopic data with reported values. The effects of the isolated compounds on lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells were investigated. Compounds 1 and 2 exhibited significant inhibitory effects on LPS-induced IL-6 and IL-12 p40 production, with IC50 values ranging from 2.7 to 6.1 muM. Compound 1 also showed a moderate inhibitory effect on LPS-stimulated production of TNF-alpha with an IC50 value of 20.1 muM. Further studies of the potential anti-inflammatory effects and benefits of flavonoids from A. membranaceus are warranted.

Absorptive constituents and their metabolites in drug-containing urine samples from Wuzhishan miniature pigs orally administered with Buyang Huanwu decoction.[Pubmed:23516044]

J Nat Med. 2014 Jan;68(1):11-21.

Buyang Huanwu decoction (BYHWD), a famous traditional Chinese medicine prescription for the treatment of cerebrovascular diseases, is composed of seven commonly used Chinese herbs--Astragali Radix, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Chuanxiong Rhizoma, Carthami Flos, Persicae Semen and Pheretima. To determine the main absorptive constituents and the metabolites of BYHWD in vivo, urine samples from Wuzhishan (WZS) miniature pigs orally administered with BYHWD (13.6 g crude drugs/kg) were collected to investigate the characteristic compounds. By comparing the high-performance liquid chromatography of a drug-containing urine sample with that of a drug-free sample, 17 characteristic compounds were isolated from the methanol extract of a drug-containing urine sample by column chromatography. Their structures, including 11 isoflavanoids, 2 pterocarpanoids and 4 isoflavonoids, were identified by spectroscopic means. Of the 17 compounds, 8 (1-8) were new compounds with the following structures: 3S-7,3',4'-trihydroxyisoflavan-3'-O-beta-D-glucuronide (1), 3S-7,3',4'-trihydroxyisoflavan-4'-O-beta-D-glucuronide (2), 3S-7,2',4'-trihydroxyisoflavan-2'-O-beta-D-glucuronide (3), 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan-2'-O-beta-D-glucuronide (4), 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan-2'-O-beta-D-glucuronide-6"-methyl ester (5), 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucuronide-6"-methyl ester (6), 3R-7,2',3'-trihydroxy-4'-methoxyisoflavan-3'-O-beta-D-glucuronide-6"-methyl ester (7), and 3S-7,4',5'-trihydroxy-2',3'-dimethoxyisoflavan-5'-O-beta-D-glucuronide (8). Based on the possible relationship and metabolic pathways of the 17 compounds in vivo, 3R-7,2'-dihydroxy-3',4'-dimethoxyisoflavan (isomucronulatol, 11), 6aR,11aR-3-hydroxy-9,10-dimethoxypterocarpan (methylnissolin, astrapterocarpan, 13), 7,3'-dihydroxy-4'-methoxyisoflavone (calycosin, 16) and 7-hydroxy-4'-methoxyisoflavone (formononetin, 17) were thought to be the most important absorptive original isoflavonoid constituents of BYHWD in vivo, which underwent reactions of glucuronidation, hydroxylation, demethylation and reduction. The other 13 compounds were deduced to be their metabolites.

A new indolizinone from Polygonatum kingianum.[Pubmed:14735451]

Planta Med. 2003 Nov;69(11):1066-8.

A new indolizinone, namely kinganone (1) together with 3-ethoxymethyl-5,6,7,8-tetrahydro-8-indolizinone (2) and isomucronulatol (3) were isolated from the rhizome of Polygonatum kingianum. Their structures were elucidated mainly on the basis of spectral data. Indolizinones 1 and 2 showed weak antibacterial and antifungal activities when compared to rifampicin and amphotericin, respectively, in the agar diffusion assay.

Bioactive flavonoids from the black locust tree, robinia pseudoacacia.[Pubmed:21214467]

Pharm Biol. 2000;38(3):229-34.

Five flavonoids, acacetin ( 1 ), secundiflorol I ( 2 ), mucronulatol ( 3 ), isomucronulatol ( 4 ), and isovestitol ( 5 ) were isolated, with the fractionation being guided by the brine shrimp lethality test (BST), from the ethanolic extract of the whole plant of Robinia pseudoacacia (Fabaceae). The structures of 1 - 5 were identified by spectral analyses. Compounds 2 - 5 are, for the first time, reported from this species. Corrections have been made for the previous literature assignments of the 13 C NMR resonances of compounds 1 - 3 . Bioactivities in BST and cytotoxicities against a panel of six solid human tumor cell lines were determined, and 1 was significantly cytotoxic in the prostate cell line (PC-3).