Schizandra Chinensis BAILL Research Articles

Antioxidant activity and hepatoprotective effect of Schizandra chinensis Baill. Extracts containing active components in alcohol-induced HepG2 cells

The antioxidant activities and hepatoprotective effects of Schizandra chinensis Baill. extracts (SCE) were evaluated. The contents of the active components schisandrin, schisandrin C, gomisin A, and gomisin N in SCE were 8.802±1.390, 1.011±0.203, 0.954±0.191, and 3.351±0.829 mg/g, respectively. The antioxidant activity of SCE was measured based on the DPPH free radical scavenging activity and the superoxide dismutase (SOD)-like activity. The IC50 values for the DPPH radical scavenging activity and SOD-like activity were 18.1 and 44.2mg/mL, respectively. The protective effect of SCE against alcohol-induced oxidative injury in HepG2 cells was investigated. Cells pretreated with SCE (100–400 μg/mL) showed an increased resistance to oxidative stress in a dose-dependent manner. Expressions of Bcl-2 and pro-caspase-3 proteins were induced by SCE in HepG2 cells. SCE can be useful for management of antioxidant and hepatoprotective effects.

Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Context: Schizandra chinensis Baill (Magnoliaceae) fruit extract (SCE) is considered a traditional herbal medicine for the treatment and alleviation of various diseases. Gastric cancer is the second most common cause of cancer-related death worldwide, and the first most common in Korea.Objectives: This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells.Materials and methods: SCE concentrations from 100 to 400 µg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes.Results: SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% ± 5.2% at 100 µg/ml and 87.3% ± 7.6% at 400 µg/ml at 24 h and by 40.2% ± 5.3% 100 µg/ml and 95.3% ± 1.3% 400 µg/ml at 72 h) and increased the sub-G1 phase (25.3% ± 5.2% at 100 µg/ml and 370.2% ± 7.2% at 400 µg/ml) and the mitochondrial membrane depolarization (11.2% ± 2.1% at 100 µg/ml and 311.5% ± 6.1% at 400 µg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death.Discussion and conclusion: These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.

Phenylpropanoids as the biologically active compounds of the medicinal plants and phytopharmaceuticals

In the present paper are discussed the results of the investigations of the phenylpropanoids of the medicinal plants which are of the great interest as the sources of the neurotropic, adaptogenic, immunostimulating, antioxidative, and hepatoprotective preparations. There were shown the necessity of using of the standard samples of triandrin (Rhodiola rosea L. tissue cultures, Salix viminalis L. barks), rosavin (Rhodiola rosea L. rhizomes), syringin, or eleutheroside B [Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. rhizomes, Syringa vulgaris L. barks], and silybin [Silybum marianum (L.) Gaertn. fruits] for purpose of the standardization of the corresponding drugs and pharmaceuticals. It was shown also the significance of γ-schizandrin, chicoric acid, rosmarinic acid and lavandoside for purposes of the standardization of raw material and preparations of Schizandra chinensis Baill. fruits and seeds, Echinacea purpurea (L.) Moench. herbs, Melissa officinalis L. herbs and Lavandula spica L. flowers respectively.

Anti-diabetic effect of a traditional Chinese medicine formula

An anti-diabetic TCM formula consisting of Schizandra chinensis Baill. (SC), Coptis chinensis (CC), Psidium guajava L. leaves (PG) and Morus alba L. leaves (MA) was developed based on its α-glucosidase, DPP-4 and AGE inhibitory activities in vitro using response surface methodology (RSM). Then, the in vivo study was carried out to confirm the anti-diabetic function of the formula. RSM results showed that the optimum anti-diabetic TCM formula is the combination SC (3000 μg mL(-1)), CC (80 μg mL(-1)), PG (374.56 μg mL(-1)) and MA (480 μg mL(-1)). For the in vivo study, insulin resistant mice were induced by high-fat/high-sucrose (HF/HS) feeding for 6 weeks. Administration of the developed formula significantly decreased non-fasting blood glucose in the HF/HS diet mice. Moreover, the formula decreased blood glucose levels in the insulin tolerance test. These results indicated that the anti-diabetic mechanism of the formula might be due to decreased insulin resistance. The serum fructosamine level in the high dose group was significantly lower than the HF/HS and normal control groups, indicating that the formula could improve middle term glucose levels and reduce the risk of complications. The contents of berberine and 1-deoxynojirimycin in the formula were 4.7 ± 0.4 and 77.1 ± 1.1 μg mL(-1), respectively. These two compounds can be used as indicators for quality control during production.

오미자에서 분리된 dibenzocyclooctadiene lignan의 일종인 gomisin N에 의한 인체혈구암세포의 세포주기 G1 arrest 유발

본 연구에서는 오미자에서 분리된 dibenzocyclooctadiene lignan의 일종인 gomisin A와 gomisin N에 대한 항암효능을 U937 인체혈구암세포를 대상으로 조사하였다. Gomisin N은 처리농도의 증가에 따라 U937 세포의 증식을 억제하였으나 동일조건에서 gomisin A는 세포독성 효과를 나타내지 못하였으며, gomisin N에 의한 U937 세포의 증식억제는 세포주기 G1 arrest 유발에 의한 것이었다. Gomisin N에 의한 G1 arrest는 cyclin E, cyclin-dependent kinase (Cdk) 2 및 Cdk4의 발현 억제와 Cdk inhibitor인 p16 (INK4A) 및 p21 (WAF1/CIP1)의 발현 증가와 연관성이 있었으나, gomisin A는 세포주기 인자들의 발현에 유의적인 변화를 유발하지 않았다. 또한 gomisin N은 retinoblastoma 단백질군인 pRB 및 p130의 인산화를 억제하였으며, 전사조절인자인 E2F 단백질들의 발현을 억제하였다. 본 연구의 결과에서 gomisin N에 의한 U937 세포의 증식억제는 세포주기 조절인자들의 발현 변화를 통한 G1 arrest 유발에 의한 것임을 알 수 있었으며, gomisin N은 암예방 및 항암활성 후보불질로서의 개발 가능성이 있음을 알 수 있었다. We investigated the anti-cancer effects of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in human promyelocytic U937 cells. Gomisin N, but not gomisin A, inhibited cell growth in a concentration-dependent manner, which was associated with the induction of G1 arrest of the cell cycle. G1 arrest induced by gomisin N was correlated with down-regulation of cyclin E, cyclin-dependent kinase (Cdk) 2 and Cdk4, and a concomitant up-regulation of Cdk inhibitors such as p16 (INK4A) and p21 (WAF1/CIP1). Furthermore, gomisin N inhibited phosphorylation of retinoblastoma protein (pRB) and p130, and expression of transcription factor E2Fs. The results indicated that growth inhibition by gomisin N is related to cell cycle arrest at G1 in U937 cells and these findings suggest that gomisin N may be a useful chemotherapeutic agent.

Apoptosis induction of human leukemia U937 cells by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill

We compared the pro-apoptotic effect of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in U937 human promyelocytic leukemia cells in vitro. Gomisin N, but not gomisin A, inhibited cell growth in a dose-dependent manner, which was associated with the induction of apoptosis. The increase in apoptosis that was induced by gomisin N was correlated with down-regulation of anti-apoptotic Bcl-2 expression, a decrease in the mitochondrial membrane potential (MMP) and a release of cytochrome c from the mitochondria into the cytosol. Furthermore, gomisin N induced the proteolytic activation of caspase-9 and -3 and a concomitant degradation of poly(ADP-ribose) polymerase. However, caspase-8 was not activated and cleavage of Bid was not observed in gomisin N-treated U937 cells. The cytotoxic effects and apoptotic characteristics induced by gomisin N were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role that caspase-3 plays in the process. We conclude that gomisin N induces the apoptosis of U937 cells through a signaling cascade of mitochondria-mediated intrinsic caspase pathways and gomisin N may be a useful chemotherapeutic agent.

Salmonella gallinarum와 Staphylococcus epidermidis 균주에 대한 한약재의 항균 활성

The present study was conducted to investigate the antimicrobial activities of extracts from approximately 40 different traditional Korean medicinal herbs against S. gallinarum and S. epidermidis. The extracts from Schizandra chinensis Baill., Melia azedarach Linne, Caesalpinia sappan Linne. and Rhus javanica Linne. exhibited high antimicrobial activities against S. gallinarum, whereas the extracts from Melia azedarach Linne and Rhus javanica Linne. exhibited high antimicrobial growth for S. epidermidis. Minimum inhibitory concentrations (MIC) of Melia azedarach Linne, Caesalpinia sappan Linne. and Rhus javanica Linne. for S. gallinarum were 1.2 mg/mL, whereas MIC of exracts from Rhus javanica Linne. extract for S. epidermidis were 0.6 mg/mL. Heat treatment of the extracts from Schizandra chinensis Baill. and Rhus javanica Linne. caused a significant reduction in antimicrobial activities against S. gallinarum. but didn't affect antimicrobial activities against S. edidermidis. Alkaline treatment of the extracts from Schizandra chinensis Baill. caused a significant reduction in antimicrobial activities against S. gallinarum, while similar treatment of the extracts from Rhus javanica Linne. caused a significant increase in antimicrobial activities against S. edider- midis. Since extracts from Rhus javanica Linne. and Caesalpinia sappan Linne. exhibited the highest antimicrobial activities, these extracts at the concentrations of 100, 300 or 500 ppm were added and then bacterial growth-inhibiting activities for S. gallinarum and S. epidermidis by these two extracts were further examined. Optical density at 620 nm (OD620) after 24 hours incubation in the absence of Rhus javanica Linne. extract ranged from 0.30 to 0.45 compared with OD620 value ranging from 0.06 to 0.18 in the presence of 100, 300 or 500 ppm of the extract, indicating that growth of all bacteria was significantly inhibited within 24 hours by the addition of at least 100 ppm of Rhus javanica Linne extract. Value of OD620 after 24 hours incubation in the absence of Caesalpinia sappan Linne. extract ranged from 0.30 to 0.55 compared with OD620 value ranging from 0.05 to 0.15 in the presence of 300 or 500 ppm of the extract, indicating that growth of all bacteria was also significantly inhibited within 24 hours by the addition of at least 300 ppm of Caesalpinia sappan Linne. extract. In conclusion, these findings suggest that extracts from Rhus javanica Linne. and Caesalpinia sappan Linne. may play important roles in antimicrobial activities against S. gallinarum and S. epidermidis.

Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells

We isolated two phytochemical lignans, schisandrin and schisandrin C, from Schizandra chinensis Baill and investigated their anti-cancer effects in human leukemia U937 cells. Schisandrin C inhibited cell growth in a dose-dependent manner, which was associated with the induction of G1 arrest of the cell cycle and apoptosis; schisandrin did not inhibit growth. Schisandrin C induced G1 arrest was correlated with down-regulation of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk) 4 and E2Fs expression, inhibition of phosphorylation of retinoblastoma protein (pRB), and up-regulation of the Cdk inhibitor p21(WAF1/CIP1). In addition, schisandrin C-induced apoptosis was associated with down-regulation of expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, proteolytic activation of caspase-3 and -9, and a concomitant degradation of poly(ADP-ribose) polymerase (PARP). Furthermore, schisandrin C-induced apoptosis was significantly inhibited by a caspase-3 specific inhibitor z-DEVD-fmk, indicating an important role for caspase-3 in the schisandrin C mechanism. In summary, growth inhibition by schisandrin C is related to cell cycle arrest at G1 and induction of caspase-3-dependent apoptosis in U937 cells; these findings suggest that schisandrin C may be a useful chemotherapeutic agent.

Influence of the Plant Extract Complex “AdMax” on Global Gene Expression Levels in Cultured Human Fibroblasts

Ethanol/water extracts from roots of Leuzea carthamoides Iljin, Rhodiola rosea L., Eleutherococcus senticosus Maxim, and from dry berries of Schizandra chinensis Baill. are known as adaptogenic remedies, which enhance physical endurance, counteract fatigue and restore suppressed immunity. Molecular mechanisms underlying effects of the extracts are poorly understood. In this study, a combination of these four extracts called AdMax™ (Nulab, Inc., Florida) was examined for its ability to influence gene expression levels in cultured human fibroblasts in vitro with the help of whole-genome Affymetrix oligonucleotide microarrays. We showed that AdMax treatment results in significant changes (at least 2 fold, p <. 05) in expression of 67 genes that are involved in metabolism of protein, nucleic acids, lipid and carbohydrates, in regulation of transcription, protein and ion transport, response to stimulus and stress. Enhancing expression of the PANK2 gene is of special interest in connection with AdMax ability to enhance physical endurance and counteract fatigue. PANK2 encodes a mitochondrial enzyme pantothenate kinase 2, which provides coenzyme A biosynthesis and thereby plays crucial role in energy metabolism. Partial deficiency of PANK2 gene activity leads to pantothenate kinase-associated neurodegeneration. In this connection potential therapeutic use of AdMax in patients with neurodegenerative diseases is discussed.

Inhibitory Effect of Schizandrin on Passive Cutaneous Anaphylaxis Reaction and Scratching Behaviors in Mice

To evaluate the antiallergic effect of the fruit of Schizandra chinensis Baill (Family Magnoliaceae), which inhibited the mouse passive cutaneous anaphylaxis (PCA) reaction in a preliminary experiment, its main constituent, schizandrin, was isolated and its antiallergic effect investigated. Schizandrin inhibited the PCA reaction induced by the IgE-antigen complex, the scratching behaviors induced by compound 48/80 and the serum IgE production induced by ovalbumin. Schizandrin also inhibited the in vitro degranulation of compound 48/80-induced rat peritoneal mast cells and IgE-induced RBL 2H3 cells. Schizandrin reduced the protein expressions of TNF-alpha and IL-4 in IgE-induced RBL 2H3 cells. These findings suggest that schizandrin can improve IgE-induced anaphylaxis and scratching behaviors.

홍화씨와 한약재 흔합추출물이 Streptozotocin으로 유도한 흰쥐의 혈당과 혈액 성분에 미치는 영향

당뇨병은 생체내 당 이용 능력의 이상으로 일어나는 만성대사성 질환으로서 심혈관계 합병증이 일으키는 대표 증상인 고혈당과 지질대사를 치료하기 위하여 많은 환자들이 민간요법에 의존하고 있다. 이에 본 연구는 홍화씨와 한약재혼합 추출물이 혈당강하와 지질상태 개선에 대한 효능을 검증하고자 실시하였다. 당뇨는 streptozotocin(45 ㎎/㎏ B.W.)으로 S.D.계 흰쥐에게 근육주사로 유도시킨 다음 주재료로 볶은 홍화씨 50 g, 100 g 각각에 부재료로 맥문동, 감초, 상엽, 백복령, 숙지황, 비파엽, 독활, 대추, 산수유, 목단피, 천화분, 오미자를 섞어서 만든 한방 혼합 추출물을 당뇨 유도 쥐에게 체중 ㎏ 당 100 ㎎, 200 ㎎의 홍화씨를 섭취할 수 있도록 각각 경구 투여하였다. 당뇨쥐의 고혈당 증상은 100 g의 홍화씨를 넣고 추출한 한약재 혼합추출물의 투여로 정상수준은 아니었지만 34% 낮아졌다(p＜0.0.5). 혈장 내 지질과산화물 함량은 정상군과 당뇨 유도군 간에 유의한 차이는 없었으나, 간 마이크로좀의 지질과산화물 함량은 정상군은 6.20±2.25 n㏖/㎎ protein에 비하여 당뇨군은 7.74 n㏖/㎎ protein로 p＜0.05 수준에서 높았다. 그러나 100 g의 홍화씨를 첨가하여 만든 한약재 혼합추출물 투여했을 때 5.85 n㏖/㎎ protein 수준까지 낮추어 주었다. 혈액과 간 조직 내 중성지방 함량은 역시 100 g의 홍화씨를 첨가하여 만든 한약재 혼합추출물 투여로 p＜0.05 수준에서 저하효과가 현저하였다(p＜0.05). 그러나 혈액과 간 조직 내 유리지방산, 총콜레스테롤과 인지질함량은 실험 전 군에서 유의적인 차이를 볼 수 없었고, 정상군에 비하여 당뇨군에서 혈장내 LDL-콜레스테롤과 동맥경화지수가 유의적으로 높은 반면에 HDL-콜레스테롤은 낮았으며 홍화씨와 한약재 혼합추출물이 이들 함량 변화에 미치는 효과는 관찰되지 않았다. 이상의 본 실험결과는 당뇨에 의한 혈당, 지질과산화물 그리고 중성지방 증가는 홍화씨와 한약재 혼합추출물의 투여로 다소 완화되었다. 이러한 결과를 바탕으로 체내 혈당조절에 의한 당뇨병의 예방 및 치유효과가 있는 홍화씨와 같은 천연물질의 기능성 성분에 대하여 향후에 보다 심층 있는 연구를 통하여 건강 기능성 식품 소재로 활용하는 것이 매우 중요할 것으로 여겨진다.

ANTICOMPLEMENTARY ACTIVITY AND COMPLETE 13C NMR ASSIGNMENT OF CITROSTADIENOL FROM SCHIZANDRA CHINENSIS

AbstractCitrostadienol was isolated from the fruits of Schizandra chinensis Baill: (Schizandraceae) by silica gel chromatography and assigned fully by spectroscopic analyses (1H-1H COSY: HMQC and HMBC). It demonstrated higher inhibition activity on classical complement pathway (IC50, 4.6 × 10−8M) than previously reported active steroids.

The constituents of Schizandra chinensis Baill. XV. Isolation and structure determination of two new lignans, gomisin S and gomisin T.

Two new dibenzocyclooctadiene lignans, gomisin S (1) and gomisin T (2), were isolated from the fruits of Schizandra chinensis BAILL.(Schizandraceae). On the basis of spectral methods and chemical transformations, the structures of 1 and 2 were elucidated as (6S, 7S, 8S, S-biar)-5, 6, 7, 8-tetrahydro-1, 2, 10, 11, 12-pentamethoxy-6, 7-dimethy1-3, 8-dibenzo [a, c] cyclooctenediol and (6S, 7S, R-biar)-5, 6, 7, 8-tetrahydro-1, 2, 10, 11, 12-pentamethoxy-6, 7-dimethy1-3, 7-dibenzo [a, c] cyclooctenediol, respectively.

The constituents of Schizandra chinensis Baill. XI. The structures of three new lignans, angeloylgomisin O, and angeloyl- and benzoylisogomisin O.

Three new dibenzocyclooctadiene lignans, angeloylgomisin O (1), and angeloyl-(2) and benzoylisogomisin O (3) were isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae). Their absolute structures were elucidated by means of chemical and spectral studies.

The constituents of Schizandra chinensis Baill. XII. Isolation and structure of a new lignan, gomisin R, the absolute structure of wuweizisu C and isolation of schisantherin D.

A new dibenzocyclooctadiene lignan, gomisin R (4), was isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae) together with wuweizisu C (1)2) and schisantherin D (12).3) The absolute structure of 1, the relative structure of which has been elucidated by Liu et al., was defined by chemical correlation with dimethylgomisin J (2). The absolute structure of 4 was determined by spectral studies and chemical correlation with 1.

The Constituents of Schizandra chinensis Baill. X. The Structures of .GAMMA.-schizandrin and four new lignans,(-)-gomisins L1 and L2,(.+-.)-gomisin M1 and (+)-gomisin M2.

Four new dibenzocyclooctadiene lignans, named (-)-gomisins L1 (6) and L3 (7), (±)-gomisin M1 (8) and (+)-gomisin M2 (9), were isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae). Their absolute structures were elucidated by means of chemical and spectral studies. The stereostructure of γ-schizandrin (1, dl-form), the plane structure of which had already been suggested by Kochetkov et al. and Liu et al., was also elucidated on the basis of chemical and spectral studies.

The constituents of Schizandra chinensis Baill. IX. The cleavage of the methylenedioxyl moiety with lead tetraacetate in benzene, and the structure of angeloylgomisin Q.

A procedure for selective cleavage of the methylenedioxyl moiety with lead tetraacetate in dry benzene is described. Piperonylic acid methyl ester (5), 4-nitro-1, 2-methylenedioxybenzene (6), 3, 4-methylenedioxytoluene (7), 2, 3-methylenedioxyanisole (8) and gomisin A (9) afforded protocatechuic acid (12), 4-nitrocatechol (13), 3, 4-dihydroxytoluene (14), 2, 3-dihydroxyanisole (15) and compound 16, respectively. The structure of angeloylgomisin Q isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae), was elucidated as 1 by using the above reaction.

The constituents of Schizandra chinensis Baill. VI. 13C nuclear magnetic resonance spectroscopy of dibenzocyclooctadiene lignans.

The 13C NMR spectra of thirteen dibenzocyclooctadiene lignans, isolated from the iruits of Schizandra chinensis BAILL. (Schizandraceae), were analyzed and their carbon shifts assigned. Several important chemical shift trends are described.

The constituents of Schizandra chinensis Baill. VII. The structures of three new lignans, (-)-gomisin K1 and (+)-gomisins K2 and K3.

Three new dibenzocyclooctadiene lignans named (-)-gomisin K1 (1) and (+)-gomisins K2 (2) and K3 (3) were isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae). Their structures were elucidated on the basis of chemical and spectral studies.

The constituents of Schizandra chinensis Baill. III. The structures of four new lignans, gomisin H and its derivatives, angeloyl-, tigloyl- and benzoyl-gomisin H.

Four new dibenzocyclooctadiene lignans, angeloyl-(1), tigloyl-(2) and benzoyl-gomisin H (3) and gomisin H (4), were isolated from the fruits of Schizandra chinensis BAILL. (Schizandraceae). Their structures were elucidated by chemical and spectral techniques.