Advances in modern research on anti-liver disease of Tibetan medicine Semen Hertospermi / 中草药

Semen Hertospermi (Bolengguazi in Chinese, BL), as well-known Tibetan medicine, is one of commonly used drugs by Tibetan healers for the treatment of liver diseases and cholic diseases. Modern research indicated that BL had multiple pharmacological effects including hepatoprotection, anti-hepatitis B virus and anti-liver fibrosis, etc. And the lignans are the major pharmacodynamic substances. The fatty acid, polysaccharides and other ingredients also have hepatoprotective effects. This article mainly reviews the pharmacodynamic substances, pharmacological effects, preparation research and development related to anti-liver disease, so as to provide reference and thinking for the research and application of BL and preparations development in the prevention of liver disease and promote the modern research and development of ethnic medicine.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions / 中国天然药物

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions / 中国天然药物

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC, C and decrease in T when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.

Herpetolide C: one new 7H-dibenzoc,eoxepin-5-one from Herpetospermum caudigerum / 药学学报

The chemical constituents of Herpetospermum caudigerum were investigated using chromatographic methods, including silica gel column chromatography, Sephadex LH-20 and semi-preparative HPLC. Four compounds were isolated and their structures were elucidated by spectral data and physicochemical properties, which were identified as 2,11-dimethoxy-3,9-dihydroxy-7H-dibenzo[c,e]oxepin-5-one (1), 7,8'-didehydroherpetotriol (2), herpetotriol (3) and kaempferitrin (4). Among those, compound 1 is one new 7H-dibenzo[c,e] oxepin-5-one, named as herpetolide C.

Formulation of dried lignans nanosuspension with high redispersibility to enhance stability, dissolution, and oral bioavailability / 中国天然药物

Herpetospermum caudigerum lignans (HTL), one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects, has limited clinical applications because of poor aqueous solubility and low bioavailability. Both herpetrione (HPE) and herpetin (HPN) are the most abundant ingredients in HTL and exhibit weak acidity. The purpose of the present study was to produce dried preparations of HTL (composed of HPE and HPN) nanosuspensions (HTL-NS) with high redispersibility using lyophilization technology. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, stability, solubility, dissolution and in vivo bioavailability. HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187. The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4% (W/V) mannitol as cryoprotectants, and had a better stability at 4 or 25 °C for 2 months, compared to HTL-NS. In the in vitro test, the dried preparations showed markedly increased solubility and dissolution velocity. Besides, in the in vivo evaluation, it exhibited significant increases in AUC, CMRT and a decrease in T, compared to the raw drug. In conclusion, our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with pH-dependent solubility.

Lignans-rich extract from Herpetospermum caudigerum alleviate physical fatigue in mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum.</p><p><b>METHODS</b>The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum (chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione (HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid (BLA), blood urea nitrogen (BUN), malondialdehyde (MDA), hepatic glycogen (HG), lactic dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) determined following the recommended procedures provided by the commercial kits.</p><p><b>RESULTS</b>Compared with the control group, the lignans extract (ethyl acetate fraction) of Herpetospermum caudigerum and HPE could signifificantly prolonged the exhaustive swimming time (P<0.05 or P<0.01), and also increased the HG levels (P<0.05 or P<0.01) and the activities of antioxidant enzymes (SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups (P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group (P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters.</p><p><b>CONCLUSIONS</b>The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.</p>

Hepatoprotective effects of total lignans of Herpetospermum caudigerum nanosuspension capsules / 中国药学杂志

OBJECTIVE: To prepare total lignans of Herpetospermumcaudigerum nanosuspension capsules (NSC), and study its hepatoprotective effect against acute live injury induced by carbon tetrachloride (CC14) in comparison with Ganneng dripping pills. METHODS: TL-NS was prepared by high pressure homogenization technique, and characterized in terms of morphology and particle size et al. The serum levels of ALT and AST and the activities of SOD and MDA in liver tissue homogenates were measured in the rat model of acute liver injury induced by intraperitoneal injection of 30% CC14, and the hepatic pathological morphology was observed by optical microscope. RESULTS: After being dissolved, NSC was irregular spheroidal as observed by scanning electron microscopy, and the other quantitative values of physical and chemical characterization were within reasonable ranges. Compared with Ganneng dripping pils, the levels of ALT, AST and MDA of the rats treated with NSC were significantly lowered, and the activities of SOD in liver tissue was increased obviously. Histological observation showed that NSC could ameliorate the histological damages induced by CC14. CONCLUSION: The hepatoprotective effects of NSC are significantly better than Ganneng dripping pils. This study provides certain reference to the dosage form development and clinical application of total lignans.