| Morus yunnanensis Koidz belongs to the the genus Morus of the family Moraceae, distributed in the northwest of Yunnan province. Many various bio-components were isolated from the genus Morus: the alcohol soluble part is mainly phenolic compounds which have antihypertension, antivirus, antibacterial, antifungi, antioxidation, anti-inflammation, and anticancer activities; the water soluble compounds are mostly amino acids, and polyhydroxylated alkaloids which have antiglycemia activity.Faeces bombycis, the larvae of silkworm (Bobyx mon L)'s dried dejecta, are written in Compendium of Materia Medica. According to the theories of traditional Chinese medicine, they are slightly bitter in taste, mild in nature, and attributive to the liver meridian. In traditional Chinese medicine, their pharmacological actions are to expel wind, dredge the meridians, and ease joint pains. And they are often contributed in folk medicine for treatment of diabetes. Our experimental results show that 60% alcohol extract of Faeces bombycis has the effects of anα-glucosidase inhibitor.By means of chromatographic and spectrographic technologies as well as chemical methods, the two medical materials mentioned above were studied systemically in chemistry and related bioassays.Forty seven compounds were obtained from 95 % alcohol extract (CH3COOC2H5 and CHCl3 extract) of the stem bark of M. yunnanensis Koidz. They were identified as follows: Yunanensol A (1), Yunanensol B (2), Yunanensin B (3), Yunanensin A (4), Yunanensin C (5), Yunanensin D (6), Yunanensin E (7), Kuwanon H (8), Kuwanon G (9), Kuwanon O (10), Sanggenol M (11), Mongolicin F (12), Guangsangon J (13), Mulberrofuran J (14), Guangsangon B (15), Guangsangon L (16), Kuwanon X (17), Kuwanon P (18), Mulberrofuran E (19), Mulberrofuran O (20), Chalcomoracin (21), Mulberrofuran K (22), Sorocein A (23), Mulberrofuran F (24), Kuwanol A (25), Albanol B (26), Mulberrofuran Q (27), Mongolicin C (28), Moracin P (29), Moracin M (30), Mulberroside C (31), Austrafuran C (32), 3',5',2,4-tetrahydroxy-4-(3-methyl-lbutenyl) Stibene (33), Resveratrol (34), Oxyresveratrol (35), Morachalcone A (36), 2',4',7-trihydroxy-(2S)-flavone (37), 5,7,2',4'-tetrahydroxy-3-gerany flavone (38), Norartocarpetin (39), Isolicoflavonol (40), Kaempferol (41), Sitosteryl 3β-glucoside 6'-O-palmitate (42), n-butanoic acid (43),β-daucosterol (44),β-sitosterol (45), Betulinic acid (46), Lupeol (47). Among them, compounds 1 and 2 are new flavones, compounds 3-6 were new Diels-Alder adducts, and 7 is a new natural product. And there are twenty-six Diels-Alder adducts (3-28), seven stilbenes (29-35), eight flavones (1, 2, 36-41), two triterpenoids (46,47) and four other compounds (42-45).Among them, all the forty seven were isolated from the stem bark of M. yunnanensis Koidz for the first time.Twenty nine compounds were obtained from 60% alcohol extract and 95% alcohol extract of Faeces bombycis. They were identified as follows: Scopoletin (1), Umbelliferone (2), Esculetin (3), Dihydro uracil (4), Uracil (5), (6S,9R)-Vomifoliol (6), (6S,9S)-Vomifoliol (7), Loliolide (8), Benzoic acid (9), 9,16-Dioxo-10,12,14-octadecatrienoic acid (10), 1-doexynojirimycin (11), Fagomine (12), Alanine (13), Glutamic acid (14), Betaine (15), Isoleucine (16), Leucine (17), Phenylalanine (18), L-pipecolinic acid (19),3S,5S-dihydroxy-6R, 7-megstigmadien-9-one (20),3S, 5R-dihydroxy-6S,7-megstigmadien-9-one (21), (6R,9R)-3-Oxo-α-ionolβ-D-glucopyranoside (22), (6R, 9S)-3-Oxo-α-ionolβ-D-glucopyranoside (23), Blumenol C glucoside (24), Byzantionoside B (25), Alangionoside L (26), Lutein (27),β-sitosterol (28),β-daucosterol (29). Among them, there are three coumarins (1-3), ten nor-sesquiterpenoids and glycosides (6-8, 20-26), two polyhydroxylated alkaloids (11, 12), five amino acids (13, 14, 16-18), four containing N compounds (4, 5, 15, 19) and four other compounds (42-45).Among them, twenty-one compounds (1-12, 15, 20-17) were isolated from Faeces bombycis for the first time.The results of bioassays displayed:1. (1) By MTT, twenty compounds (including one new Diels-Alder adduct), which were obtained from the 95% ethanol extract of M. yunnanensis Koidz, showed moderate anticancer activity against five human cancer cell lines (A549, Bel-7402, BGC-823, HCT-8, A2780) with IC50 ranging from 3.9-9.5μg/mL. (2) Twenty three phenolic compounds, isolated from the EtOAc soluble part of M. yunnanensis Koidz, inhibited the production of the lipid peroxide induced by Fe2+-Cys system in the liver microsomal obviously, with inhibitory rates more than 50% at a concentration of 10-5 mol/L,and even some of them with inhibitory rates more than 90%.(3) On the pharmacological model of release ofβ-glucuronidase from rat PMNs induced by PAF, ten compounds, isolated from M. yunnanensis Koidz, were revealed the anti-inflammation activity with the inhibitory rates more than 50% at a concentration of 10-5 mol/L. Especially two Diels-Alder adducts and two flavones (including one new flavone) revealed the inhibitory rates more than 90%.2. Two known polyhydroxy alkaloids, 1-deoxynojirimycin (11) and fagomine (12), have been isolated from the 60 % ethanol extract of Faeces bombycis by bioassay-guided fractionation using the a-glucosidase inhibitory assay. Compounds 11 and 12 exhibited IC50 values (concentration at which 50 % a-glucosidase are inhibited) of 0.014 and 1.368μg/mL,respectively. In the sucrose and starch tolerance tests, administration of 11 resulted in the hypoglycemic effect in normal and alloxan-induced diabetic mice at 9 mg/kg when dosed orally.The results from present study show that 1-deoxynojirimycin inhibits the rises of plasma glucose levels after sucrose and starch loading in mice, but no effect after glucose loading. The mechanism is that it delays the hydrolization of disaccharide into monosaccharides by inhibiting a-glucosidase on small intestine, thus delays the absorption of glucose into blood. Moreover, our study shows that compounds 11 is a selective disaccharidase inhibitor, therefore it leaves theα-amylase activity nearly unaffected and there would be less subjective symptoms for clinical use.Referring to the results in vitro it is concluded that compounds 11 is indeed the active principle of Faeces bombycis for their potent hypoglycemic effect. |
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