Acute and chronic toxicity in Sprague-Dawley rats of orally-administered total lignans from Arctii Fructus, a potential therapeutic drug for diabetes.

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.

Protective Effect of Total Lignans of Arctii Fructus on Retina in Rat Model of Type 2 Diabetes Mellitus / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of total lignans of Arctii Fructus on the retinal tissue in the rat model of type 2 diabetes mellitus. MethodWistar rats were randomized into normal， model， solvent， Shuangdan Mingmu Capsules （618 mg·kg-1）， and low-， medium-， and high-dose （100， 200， 400 mg·kg-1， respectively） total lignans of Arctii Fructus groups， with 16 rats in each group. The rat model was established by streptozotocin （STZ） combined with a high-fat diet and administrated with corresponding drugs by gavage once a day for 14 weeks. At the 14th week， blood was sampled for the collection of serum from the abdominal aorta after anesthesia， and bilateral eyeballs were collected and frozen. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of the retinal tissue in rats. The pathological changes of retinal vascular network in rats were observed by retinal vascular tissue digestion and mounting The levels of vascular endothelial growth factor （VEGF）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1） in the serum were determined by the ELISA kit. ResultCompared with the normal group， the solvent group showed pathological changes in the retinal tissue， reduced retinal ganglion cells （P<0.01）， and retinal thinning （P<0.01）， decreased E/P value in retinal blood vessels （P<0.01）， and elevated serum levels of VEGF， TNF-α， and ICAM-1 （P<0.01）. Compared with the model group， the total lignans of Arctii Fructus increased the retinal ganglion cells （P<0.01）， thickened the retina （P<0.01）， and lowered the serum levels of VEGF， TNF-α， and ICAM-1 （P<0.05， P<0.01）. ConclusionTotal lignans of Arctii Fructus may lower the VEGF， TNF-α， and ICAM-1 levels to protect the retina.

Total lignans from Vitex negundo seeds attenuate osteoarthritis and their main component vitedoin A alleviates osteoclast differentiation by suppressing ERK/NFATc1 signaling.

The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1ß (IL-1ß), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T1/2 ) was 2.82 h and 1.33 h, and the bioavailability was 15.34%-21.89% and 16.29%-22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.

Preparation and Quality Evaluation of Gastric Floating Tablets of Schisandra chinensis Total Lignans / 中国药房

OBJECTIVE：To study the prepar ation technology of gastric floating tablets of Schisandra chinensis total lignans （SCTL），and evaluate the quality of prepared tablets. METHODS ：Based on single factor test ，the orthogonal experiment was conducted to optimize the formulation of SCTL gastric floating tablets with the contents of hydroxypropylmethylcellulose （HPMC） K15M，NaHCO3 and microcrystalline cellulose as the factors ，using starting time ，holding time and cumulative release rate of gastric floating tablets as evaluation indexes. The properties ，weight difference ，floatability and accumulative release rate of the prepared SCTL gastric floating tablets were determined. The gastric floating tablets were qualitatively identified by TLC ，and the contents of schisandrin A and total lignans were determined by HPLC and UV spectrophotometry. RESULTS ：The optimal formulation of SCTL gastric floating tablets was made up of 23％ SCTL extract ，20％ HPMC K 15M，40％ microcrystalline cellulose，15％ sodium bicarbonate ，1％ octadecyl alcohol and 1％ polyvinylpyrrolidone. The results of detection of this preparation were in line with the related provisions of “0101 tablet”stated in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. TLC indicated that the chromatogram of the test sample showed the main spots of same color as the corresponding positions of the chromatogram of schizandrol A control ，Schisandra chinensis reference substance and raw material ，while the negative control has no interference. Content determination results shows that the average content of schizandrol A and total lignans in SCTL gastric floating tablets is 3.187，19.617 mg. It was preliminarily formulated that the content limitation of schizandrol A in one tablet should not be less than 2.50 mg，and the content of total lignans （calculated by schizandrol A ）should not be less than 15.50 mg. CONCLUSIONS：The preparation technology of SCTL gastric floating tablets is stable ，feasible and controllable in quality.

Evaluation of the anti-cancer potential of Cedrus deodara total lignans by inducing apoptosis of A549 cells.

BACKGROUND: Cedrus deodara (Roxb.) Loud (normally called as deodar), one out of four species in the genus Cedrus, exhibits widely biological activities. The Cedrus deodara total lignans from the pine needles (CTL) were extracted. The aim of the study was to investigate the anticancer potential of the CTL on A549 cell line. METHODS: We extracted the CTL by ethanol and assessed the cytotoxicity by CCK-8 method. Cell cycle and apoptosis were detected by a FACS Verse Calibur flow cytometry. RESULTS: The CTL were extracted by means of ethanol hot refluxing and the content of total lignans in CTL was about 55.77%. By the CCK-8 assays, CTL inhibited the growth of A549 cells in a dose-dependent fashion, with the IC50 values of 39.82 ± 1.74 µg/mL. CTL also inhibited the growth to a less extent in HeLa, HepG2, MKN28 and HT-29 cells. CONCLUSION: At low doses, the CTL effectively inhibited the growth of A549 cells. By comparison of IC50 values, we found that A549 cells might be more sensitive to the treatment with CTL. In addition, CTL were also able to increase the population of A549 cells in G2/M phase and the percentage of apoptotic A549 cells. CTL may have therapeutic potential in lung adenocarcinoma cancer by regulating cell cycle and apoptosis.

Therapeutic effects of the total lignans from Vitex negundo seeds on collagen-induced arthritis in rats.

BACKGROUND: The seeds of Vitex negundo, with rich lignans metabolites, have been widely used as a traditional Chinese medicine and Ayurvedic herbal medicine for the treatment of rheumatism and joint inflammation. The total lignans of Vitex negundo seeds (TOV) were suggested to play an important role in the treatment of arthritis. PURPOSE: The aim of the study was designed to investigate the anti-arthritic effects of TOV on collagen-induced arthritis (CIA) in rats as well as its possible mechanisms. METHODS: TOV was prepared by combined macroporous resin and polyamide column chromatography, and constituents of TOV were analyzed by HPLC. CIA model in rats was established by immunization with chicken type II collagen and then the rats were intragastrically administrated with TOV for 30 days. Rat arthritis was evaluated by measurements of hind paw edema, arthritis index score, weight growth and indices of thymus and spleen, and by histological examination. Levels of serum MMP-2, MMP-3, MMP-9, IL-1ß, IL-6, IL-8, IL-10, IL-17A and TNF-α were also examined. In addition, the expression of COX-2, iNOS and IκB, p-IκB in synovial tissues was evaluated by western blotting. The analgesic and anti-inflammatory effects of TOV were also evaluated in acetic acid-induced writhing and xylene-induced ear edema in mice, respectively. In addition, acute toxicity test was employed to preliminarily assess the safety of TOV. RESULTS: TOV significantly inhibited the paw edema and decreased the arthritis index, with no influence on the body weight and the indices of thymus and spleen of CIA rats. Meanwhile, TOV dose-dependently reduced the infiltration of inflammatory cells, synovial hyperplasia and attenuated cartilage damage. Additionally, the serum levels of IL-1ß, IL-6, IL-8, IL-17A, TNF-α, MMP-3 and MMP-9 were markedly decreased, while the level of serum IL-10 was increased in TOV-treated rats. The significant reduction of the expression of COX-2, iNOS and p-IκB and the notable increase of IκB in synovial tissues were also observed in TOV-treated animals. TOV also significantly inhibited acetic acid-induced writhing and decreased xylene-induced ear edema in mice. Finally, the maximal tolerable dose (MTD) of TOV was determined to be 16.0 g/kg. CONCLUSION: These results suggest that TOV has significant anti-arthritic effects on collagen-induced arthritis in rats, which may be attributed to the inhibition of the levels of IL-1ß, IL-6, IL-8, IL-17A, TNF-α, MMP-3 and MMP-9, and the increase of IL-10 in serum as well as down-regulation of the protein expression of COX-2 and iNOS in synovial tissues via suppressing the phosphorylation and degradation of IκB. Due to its high efficacy and safety, TOV can be regarded as a promising drug candidate for rheumatoid arthritis treatment.

New Quality Standard for Schisandrae Chinensis Fructus / 中国药师

Objective: To establish a new standard for the quality evaluation of Schisandrae chinensis Fructus. Methods: On the basis of the 2015 edition pharmacopoeia standard of Schisandrae chinensis Fructus, some testing items including the characteristic chro-matogram (HPLC) and total lignans content (UV) were established. Results: With schizandrin as the reference material, the HPLC specific chromatograms of Schisandrae chinensis Fructus including 7 characteristic peaks were established. The content of total lignans in Schisandrae chinensis Fructus was not less than 1. 8% with schizandrin as the standard. Conclusion: The proposed quality evalua-tion standard is more comprehensive and reproducible. It can provide a more scientific evaluation tool for the quality evaluation of Schisandrae chinensis Fructus and its related preparations.

[Protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride-induced liver fibrosis in rats].

This experiment was aimed to discuss the protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Forty-eight male Sprague-Dawley rats were randomly divided into the blank control group (G1), model group (G2), total lignans high, middle and low dose groups (400,200, and 100 mg•kg⁻¹â€¢d⁻¹)(G3/4/5) and the glycyrrhizin positive control group (25 mg•kg⁻¹â€¢d⁻¹)(G6), n=8 in each group. The rats in blank group received normal feeding; the rats in model group, total lignans low, middle and high dose groups and glycyrrhizic group were subcutaneously in jected with 3 mL•kg⁻¹ olive oilsolution containing 40%CCl4 every two or three days for Eight weeks. During the course, the rats inblank group and model group were orally administered with 2 mL normal saline, and the rats in total lignans groups and the glycyrrhizin positive control group received corresponding doses of drugs by intragastric administration. Eight weeks later, after the the last time modeling, the rats were sacrificed. Then the biochemical analysis was used to determine alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase (ALP) levels in serum while enzyme-linked immuno sorbent assay(ELISA) was applied for detecting transforming growth factor ß1(TGF-ß1), hyaluronic acid(HA), hydroxy-proline(HYP) and superoxide dismutase(SOD) levels in serum. HE and Masson's trichrome stainings were conducted in liver tissues to observe the pathological variations and grades of hepatic fibrosis. The results showed that as compared with the model group, the levels of ALT, AST, ALP, TGF-ß1, HA, HYP and SOD in serum of total lignans groups were significantly decreased (P<0.05, P<0.01); levels of SOD in the liver tissue homogenate were increased(P<0.05, P<0.01); the pathological damage of the liver tissues were relieved (P<0.05, P<0.01), and liver fibrosis scores were decreased(P<0.05, P<0.01). The above experimentsindicated that total lignans from Tibetan medicinal Herpetospermum seeds can effectively reduce carbon tetrachloride-induced hepatic injury of rat liver fibrosis, reduce the degree of liver fibrosis, and its mechanism maybe associated with down-regulating TGF-ß1 expression.

Effects of total lignans from tibetan medicine herpetospermum pedunculosum seeds on proliferation and apoptosis of rat hepatic stellate cells / 中草药

Objective To observe the possible mechanism of total lignans from Herpetospermum pedunculosum seeds (TLHPS) in fighting against hepatic fibrosis of hepatic stellate cell-T6 (HSC-T6) by studying the effects of TLHPS on inhibiting proliferation and inducing apoptosis of HSC-T6. Methods The cells were divided into totally six groups such as control group, TLHPS groups (10, 20, 30, 40 μg/mL), and colchicine positive control group (0.1 μg/mL). HSC-T6 cells were cultivated for 24, 48, and 72 h by six groups of culture medium containing different drugs. The proliferation inhibitory rate of HSC-T6 cells was detected by CCK8 method at 24, 48, and 72 h respectively. The apoptotic rate and cell cycle were detected by flow cytometry. Protein expression levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and transcription factors-κB (NF-κB) were detected by Western blotting. Results Compared with control group, 24, 48, and 72 h proliferation inhibitory rate of HSC-T6 was obviously elevated in TLHPS 10, 20, 30, 40 μg/mL groups (P 0.05), cell numbers in S phase obviously decreased (P < 0.01). Compared with control group, Bal-2 protein expression obviously decreased in TLHPS 10, 20, 30, 40 μg/mL groups (P < 0.05, 0.01), Bax protein expression obviously increased in TLHPS 40 μg/mL group (P < 0.01) and NF-κB protein expression obviously decreased in TLHPS 20, 30, 40 μg/mL groups (P < 0.01). Conclusion The mechanism of total lignans from Tibetan medicine Herpetospermum fighting against hepatic fibrosis might be associated with inhibiting proliferation and inducing apoptosis of HSC-T6. The inhibition of hepatic stellate cells proliferation and induction of its apoptosis may be related to lowering the expression of Bcl-2 and NF-κB.

Protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride-induced liver fibrosis in rats / 中国中药杂志

This experiment was aimed to discuss the protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Forty-eight male Sprague-Dawley rats were randomly divided into the blank control group (G1), model group (G2), total lignans high, middle and low dose groups (400,200, and 100 mg•kg⁻¹•d⁻¹)(G3/4/5) and the glycyrrhizin positive control group (25 mg•kg⁻¹•d⁻¹)(G6), n=8 in each group. The rats in blank group received normal feeding; the rats in model group, total lignans low, middle and high dose groups and glycyrrhizic group were subcutaneously in jected with 3 mL•kg⁻¹ olive oilsolution containing 40%CCl4 every two or three days for Eight weeks. During the course, the rats inblank group and model group were orally administered with 2 mL normal saline, and the rats in total lignans groups and the glycyrrhizin positive control group received corresponding doses of drugs by intragastric administration. Eight weeks later, after the the last time modeling, the rats were sacrificed. Then the biochemical analysis was used to determine alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase (ALP) levels in serum while enzyme-linked immuno sorbent assay(ELISA) was applied for detecting transforming growth factor β1(TGF-β1), hyaluronic acid(HA), hydroxy-proline(HYP) and superoxide dismutase(SOD) levels in serum. HE and Masson's trichrome stainings were conducted in liver tissues to observe the pathological variations and grades of hepatic fibrosis. The results showed that as compared with the model group, the levels of ALT, AST, ALP, TGF-β1, HA, HYP and SOD in serum of total lignans groups were significantly decreased (P<0.05, P<0.01); levels of SOD in the liver tissue homogenate were increased(P<0.05, P<0.01); the pathological damage of the liver tissues were relieved (P<0.05, P<0.01), and liver fibrosis scores were decreased(P<0.05, P<0.01). The above experimentsindicated that total lignans from Tibetan medicinal Herpetospermum seeds can effectively reduce carbon tetrachloride-induced hepatic injury of rat liver fibrosis, reduce the degree of liver fibrosis, and its mechanism maybe associated with down-regulating TGF-β1 expression.

Effects of total lignans of Schisandra chinensis on memory impairment in rats with Alzheimer's disease / 国际中医中药杂志

Objective To study the effects of total lignans of Schisandra chinensis on memory impairment in rats with Alzheimer's disease, and to discuss its mechanism of action. Methods The rats were randomly into the blank control group, the sham injury group, the pathological model group, the low dose group of Schisandra chinensis and the high dose group of Schisandra chinensis with 15 rats in each group. The animals were given medicine at 3 days after the model establishment. The ainimals of the pathological model group, the low dose group of Schisandra chinensis and the high dose group of Schisandra chinensis established the AD model by D-gal intraperitoneal injection of compound Aβ hippocampal localization injection. The low dose group of Schisandra chinensis and the high dose group of Schisandra chinensis were administrated by means of intragastric administration 1mL physiological saline containing Schisandra chinensis total lignans 50 mg×kg-1×d-1 and 100 mg×kg-1×d-1, and the blank control group, the sham injury group, the pathological model group were administrated 0.9% Sodium Chloride Injection 1 ml×d-1by means of intragastric administration. After two weeks of continuous administration, the behavioral tests were carried out on the experimental animals, and the expressions of caspase-3, Bax, Bcl-2 and mRNA in the hippocampus of rats were measured by RT-PCR. Results Compared with the pathological model group,the escape latency shortened of the low dose group and the high dose group of Schisandra chinensis were significantly shortened (P<0.05). The number of traversing platforms (3.82 ± 1.23, 5.82 ± 1.18 vs. 2.13 ± 1.48), the percentage of swimming time (39.43% ± 7.12%, 48.63% ± 7.15% vs. 59.98% ± 6.13%) of the low dose group and the high dose group of Schisandra chinensis significantly decreased (P<0.05). Compared with the pathological model group, the expression of caspase-3(6.11 ± 1.25,4.42 ± 1.13 vs.7.88 ± 1.28)and Bax mRNA(5.84 ± 1.62,4.63 ± 1.51 vs.7.54 ± 2.14) significantly decreased (P<0.05), and the expression of the Bcl-2 mRNA(1.73 ± 0.82, 3.04 ± 1.29 vs. 0.93 ± 0.62) wese increased (P<0.05). Conclusions The diatomite Soxhlet extraction method is suitable for the isolation and purification of total lignans from Schisandra chinensis, and the total lignans of Schisandra chinensis can up-regulate the expression of Bcl-2, down-regulate the expression of caspase-3 and Bax, inhibit the apoptosis of neurons induced by A beta, improve the memory impairment of AD animal models, and the intervention effect is dose dependent.

Optimization of Extraction Process for Total Lignans from Fructus Chinensis by Orthogonal Test / 中国药师

Objective:To optimize the extraction process of the total lignans from Fructus chinensis. Methods:The comprehensive weighted score method for the extraction rate and the extraction content was regarded as the index by orthogonal experimental method, the effects of ethanol concentration, extraction duration, amount of ethanol and extraction times on the extraction of the total lignans from Fructus chinensis were studied. The chromatographic separation was performed on a Unitary C18 column (250 mm × 4. 6 mm,5μm). Methanol(A)-water(B) was used as the mobile phase (0-10 min:70% A;10-13 min:70% A-85% A;13-30 min:85% A). The detection wavelength was set at 217 nm, the column temperature was maintained at 30℃,the flow rate was 1. 0 ml·min-1 and the sample size was 10μl. Results:The extraction conditions of the total lignans were as follows:14-fold amount of 85% ethanol was used for 3 times extraction with 2. 5 h for each time. Under the above conditions, the extraction rate of Schisandra lignans was 1. 10%, and the extraction content was 22. 99%. Conclusion:The extraction and purification technology for Schisandra lignans and the total poly-saccharides is stable and reliable, which provides scientific basis for the reform of Shengmai new dosage forms.

Study on Purification and Anti-inflammatory Effects of Total Lignans in Myristicae Semen / 中国中医药信息杂志

Objective To optimize purification technology of total lignans in Myristicae Semen; To study its anti-inflammatory effects. Methods Macroporous adsorption resin was used for enrichment and purification of total lignans in Myristicae Semen, with adsorption rate, desorption rate and content of total lignans as indexes. The resin type, concentration of eluent, sample weight and dosage of eluen were investigated. Anti-inflammatory effects were studied by determining swelling degree and inhibition rate of mice with ear swelling induced by xylene. Results Purification technology of total lignans was processed on type of AB-8 resin. 1 g crude extract was dissolved as sample; 40 mL preprocessed resin including 16 g resin was added and static adsorpted for 12 hours; 30% ethanol was used firstly to elute to colorless and then 300 mL 70% ethanol was used to elute; the eluent of 70% ethanol was collected. The purity of total lignans was 45.8%. There was statistical significance in ear swelling degree of total lignans in Myristicae Semen high-, medium-, and low-dosage groups compared with model group (P<0.05). Conclusion The purification technology of total lignans is stable and reproducible, and total lignans in Myristicae Semen has significant anti-inflammatory activity.

Optimization of Bran-roasted Processing Technology of Sliced Myristicae Semen by Orthogonal Test / 中国中医药信息杂志

Objective To optimize the processing technology of sliced Myristicae Semen. Methods Roasting temperature, roasting time and the amount of bran were set as factors, and the content of total lignans, volatile oil, fatty oil were set as evaluation indicators. The processing technology of sliced Myristicae Semen was optimized by L9(34) orthogonal test. Results The optimal processing technology was as following: 40 g bran plus 100 g sliced Myristicae Semen, roasting for 20 minutes at 110-120 ℃. Conclusion The process is reasonable and reliable, which can provide references for new processing technology of Myristicae Semen.

Optimization of the Extraction Technology of Total Lignans from Pine Needles of Cedrus deodara by Re-sponse Surface Methodology / 中国药房

OBJECTIVE:To optimize the extraction technology of total lignans from pine needles of Cedrus deodara. METH-ODS:Using ethanol volume fraction,ratio of liquid to solid and extraction time as response factor,the content of total lignans as response value,the response surface methodology test was conducted based on Box-Behnken design to optimize the extraction tech-nology of total lignans from pine needles of C. deodara. RESULTS:The optimal extraction technology was as follows as ethanol volume fraction of 78%,ratio of liquid to solid 25∶1,extraction time 1.75 h. The content of total lignans from pine needles of C. deodara was 99.2 mg/g,which was close to predicted value 100.49 mg/g,with relative deviation of 0.65%. CONCLUSIONS:Op-timized extraction technology of pine needles of C. deodara by response surface methodology is feasible and stable,and has good predictability.

Evaluation of hypoglycemic activity of total lignans from Fructus Arctii in the spontaneously diabetic Goto-Kakizaki rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Arctii, called "Niubangzi" in China (Great burdock achene in English), is a well-known Chinese Materia Medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions. Meanwhile it has been utilized extensively in a number of classical drug formulas as a major component for the treatment of noninsulin-dependent diabetes mellitus. It has also been reported recently that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. The aim of this study was to investigate hypoglycemic activity of total lignans from Fructus Arctii (TLFA) in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and the mechanism of its hypoglycemic activity. MATERIALS AND METHODS: Male GK rats and normal Wistar rats were used in this study, GK rats fed twice daily were given TLFA (300 mg/kg) or nateglinide (50mg/kg) orally before each meal for 12 weeks. Besides common evaluation indexes of hypoglycemic activity such as blood glucose level, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters such as cholesterol (CHOL), triglycerides (TG), et al., in rat serum. The effects of TLFA on insulin secretion and pancreas tissue sections, the levels of serum glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the α-glucosidase inhibitory activity of TLFA in vitro were investigated. RESULTS: TLFA demonstrated stable and long-lasting hypoglycemic activity in GK rats and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. Both TLFA and nateglinide controlled the glycosylated hemoglobin levels of the experimental animals very well. Stimulation of insulin secretion was proved to be one of the hypoglycemic mechanism of TLFA, promoting the release of GLP-1 should be another one, and ɑ-glucosidase inhibitory activity of TLFA also contributes to its hypoglycemic activity. In this study, we didn't found that TLFA could effect the body weight of GK rats, which was also verified by the changes of biochemical parameters of blood in experimental rats. CONCLUSION: The results of this study indicates that TLFA has significant hypoglycemic potential in GK rats, and it may be acting through stimulating insulin secretion, promoting the release of GLP-1, and decreasing intestinal absorption of glucose.

Optimization of Reflux Extraction for Total Lignans from Acanthopanax Sessiliflorus by Orthogonal Experi-ment / 中国药师

Objective:To study the optimal process of reflux extraction for lignans from Acanthopanax sessiliflorus roots. Methods:Sesamin as the reference substance, a colorimetric method was used to detect the absorption value of the samples at 558 nm to calculate the content directly. The extraction time, the extraction times and the volume of extraction solvent were applied to optimize the extrac-tion conditions for total lignans by orthogonal experiment. Results:The absorbance had a linear relationship with the amourt of sesamin within the range of 10. 6-53. 0 μg·ml-1(r=0. 999 7). The average recovery of sesamin was 102. 2%(RSD=1. 6%, n=6). The content of total lignans (measurement by sesamin) in the extracts was 10. 0 mg·g-1. The optimum reflux extraction conditions were as follows:adding 40-fold 50 % methanol, extracting once for 30 min. Conclusion:The UV method for determining the total lignans is feasible, stable and reliable as well as precise, and the optimal extraction process is reasonable.