Isolation of Anti-Diabetic Active Compounds from Benincasae Exocarpium and Development of Simultaneous Analysis by HPLC-PDA.

Diabetes is a chronic metabolic disease that is a constant problem. Previous studies have reported that Benincasa cerifera Savi. extracts are effective in treating diabetes and its complications. Benincasae Exocarpium (BE) is a fruit peel of B. cerifera that has been reported to be used for the prevention and treatment of metabolic diseases such as hyperglycemia, obesity, and hyperlipidemia. However, there are not enough studies on the compounds and bioassays to support the efficacy of BE. The inhibitory activity of the BE extracts and fractions against advanced glycation end-products (AGE) formation and α-glucosidase activity was evaluated. These assays are relevant for the treatment of type 2 diabetes and its complications. Based on these results, compounds 1-11 were isolated through bioassay-guided isolation. In addition, we developed a high-performance liquid chromatography (HPLC) method that can simultaneously analyze these 11 compounds. Activity evaluation of the compounds was also conducted, and eight compounds exhibited significant activity. Among these, flavonoid compounds showed strong activity. A quantitative evaluation of eight bioactive compounds (2, 5-11) was conducted. In conclusion, this study demonstrated the potential of BE for prevention and treatment of type 2 diabetes and its complications.

Anti-Inflammatory Activity and Mechanism of Isookanin, Isolated by Bioassay-Guided Fractionation from Bidens pilosa L.

Bidens pilosa L. (Asteraceae) has been used historically in traditional Asian medicine and is known to have a variety of biological effects. However, the specific active compounds responsible for the individual pharmacological effects of Bidens pilosa L. (B. pilosa) extract have not yet been made clear. This study aimed to investigate the anti-inflammatory phytochemicals obtained from B. pilosa. We isolated a flavonoids-type phytochemical, isookanin, from B. pilosa through bioassay-guided fractionation based on its capacity to inhibit inflammation. Some of isookanin's biological properties have been reported; however, the anti-inflammatory mechanism of isookanin has not yet been studied. In the present study, we evaluated the anti-inflammatory activities of isookanin using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We have shown that isookanin reduces the production of proinflammatory mediators (nitric oxide, prostaglandin E2) by inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Isookanin also inhibited the expression of activator protein 1 (AP-1) and downregulated the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-jun NH2-terminal kinase (JNK) in the MAPK signaling pathway. Additionally, isookanin inhibited proinflammatory cytokines (tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß)) in LPS-induced THP-1 cells. These results demonstrate that isookanin could be a potential therapeutic candidate for inflammatory disease.

Acanthopanax henryi: Review of Botany, Phytochemistry and Pharmacology.

Acanthopanax henryi (Oliv.) Harms (Araliaceae), also known as Eleutherococcus henryi and Caoyewujia (Hengliwujia) in Chinese, is a widely used traditional Chinese herb with the effects of expelling wind and removing dampness, relaxing the muscles and stimulating the blood circulation, and regulating the flow of qi to alleviate pain in the theory of Traditional Chinese Medicine. Acanthopanax henryi (AH, thereafter) possesses ginseng-like activities and is known as ginseng-like herb. In the past decade, a great number of phytochemical and pharmacological studies on AH have been carried out. Several kinds of chemical compositions have been reported, including terpenoids (monoterpenoids, diterpenoids, and triterpenoid saponins), phenylpropanoids, caffeoyl quinic acid derivatives, flavonoids, lignans, sterols, fatty acids, etc., among which, triterpenoid saponins were considered to be the most active components. Considerable pharmacological experiments in vitro have demonstrated that AH possessed anti-neuroinflammatory, anti-adipogenic, anti-inflammatory, antibacterial, anti-cancer, anti-oxidation, anti-AChE, anti-BuChE, and antihyaluronidase activities. The present review is an up-to-date and comprehensive analysis of the botany, phytochemistry, and pharmacology of AH.

Bioassay-Guided Isolation of Anti-Alzheimer Active Components from the Aerial Parts of Hedyotis diffusa and Simultaneous Analysis for Marker Compounds.

Previous studies have reported that Hedyotis diffusa Willdenow extract shows various biological activities on cerebropathia, such as neuroprotection and short-term memory enhancement. However, there has been a lack of studies on the inhibitory activity on neurodegenerative diseases such as Alzheimer's disease (AD) through enzyme assays of H. diffusa. Therefore, H. diffusa extract and fractions were evaluated for their inhibitory effects through assays of enzymes related to AD, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), and on the formation of advanced glycation end-product (AGE). In this study, ten bioactive compounds, including nine iridoid glycosides 1-9 and one flavonol glycoside 10, were isolated from the ethyl acetate and n-butanol fractions of H. diffusa using a bioassay-guided approach. Compound 10 was the strongest inhibitor of cholinesterase, BACE1, and the formation of AGEs of all isolated compounds, while compound 5 had the lowest inhibitory activity. Compounds 3, 6, and 9 exhibited better inhibitory activity than other compounds on AChE, and two pairs of diastereomeric iridoid glycoside structures (compounds 4, 8, and 6, 7) showed higher inhibitory activity than others on BChE. In the BACE1 inhibitory assay, compounds 1-3 were good inhibitors, and compound 10 showed higher inhibitory activity than quercetin, the positive control. Moreover, compounds 1 and 3 were stronger inhibitors of the formation of AGE than aminoguanidine (AMG), the positive control. In conclusion, this study is significant since it demonstrated that the potential inhibitory activity of H. diffusa on enzymes related to AD and showed the potential use for further study as a natural medicine for AD treatment on the basis of the bioactive components isolated from H. diffusa.

Inhibitory Effects of Bioassay-Guided Isolation of Anti-Glycation Components from Taraxacum coreanum and Simultaneous Quantification.

Inhibition of the formation of advanced glycation end products (AGEs) is an attractive strategy in diabetes treatment. Taraxacum coreanum extracts were suggested to have antidiabetic effects. However, studies on the components of T. coreanum are lacking, and there is no report on the inhibitory effects of T. coreanum on the formation of AGEs. Therefore, T. coreanum extracts and fractions were tested for their inhibitory effects on α-glucosidase and AGEs formation in two systems (bovine serum albumin (BSA)⁻glucose and BSA⁻methylglyoxal (MGO)). Bioassay-guided isolation of compounds from T. coreanum led to six flavones (1⁻6) and four hydroxycinnamic acid derivatives (7⁻11). Compound 11 exhibited the highest inhibitory activity against α-glucosidase and AGEs formation and had the highest content in T. coreanum extract. All compounds except compound 9 showed a stronger inhibition than the positive control in the BSA-glucose and BSA-MGO system. In addition, T. coreanum showed a higher content of bioactive compounds and stronger inhibition of AGE formation and α-glucosidase activity than T. officinale. Our study demonstrated the preventive and therapeutic efficacy of T. coreanum and its potential use as a cost-effective phytopharmaceutical in complementary therapy against type-2 diabetes and its complications.

Inhibitory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid on lipopolysaccharide-induced TNF-α, IL-1ß, and the high mobility group box 1 release in macrophages.

We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1ß at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.

Artemisia Iwayomogi Extract Attenuates High-Fat Diet-Induced Hypertriglyceridemia in Mice: Potential Involvement of the Adiponectin-AMPK Pathway and Very Low Density Lipoprotein Assembly in the Liver.

This study aimed to examine the protective effect of Artemisia iwayomogi extract (AI) against hypertriglyceridemia induced by a high-fat diet (HFD) in mice and to uncover the underlying molecular mechanisms. C57BL/6N mice were fed chow, HFD, HFD + 0.1% AI, HFD + 0.25% AI, or HFD + 0.5% AI for 10 weeks. The addition of 0.25% and 0.5% AI resulted in dose-dependent improvements in the major parameters of hypertriglyceridemia, including plasma triglyceride, free fatty acids, apolipoprotein B, and lipoprotein lipase, with parallel reductions in body weight gain, hepatic lipid accumulation, and insulin resistance. These beneficial effects were accompanied by the activation of adiponectin-adenosine monophosphate-activated protein kinase (AMPK) mediated signaling cascades in the liver, which downregulated molecules involved in lipogenesis and concurrently upregulated molecules related to fatty acid oxidation. The downregulation of molecules involved in very low density lipoprotein assembly, which was associated with improved hepatic insulin signaling, also appeared to contribute to the AI-induced attenuation of hypertriglyceridemia.

Chemical Constituents of Smilax china L. Stems and Their Inhibitory Activities against Glycation, Aldose Reductase, α-Glucosidase, and Lipase.

The search for natural inhibitors with anti-diabetes properties has gained increasing attention. Among four selected Smilacaceae family plants, Smilax china L. stems (SCS) showed significant in vitro anti-glycation and rat lens aldose reductase inhibitory activities. Bioactivity-guided isolation was performed with SCS and four solvent fractions were obtained, which in turn yielded 10 compounds, including one phenolic acid, three chlorogenic acids, four flavonoids, one stilbene, and one phenylpropanoid glycoside; their structures were elucidated using nuclear magnetic resonance and mass spectrometry. All solvent fractions, isolated compounds, and stem extracts from plants sourced from six different provinces of South Korea were next tested for their inhibitory effects against advanced glycation end products, as well as aldose reductase. α-Glucosidase, and lipase assays were also performed on the fractions and compounds. Since compounds 3, 4, 6, and 8 appeared to be the superior inhibitors among the tested compounds, a comparative study was performed via high-performance liquid chromatography with photodiode array detection using a self-developed analysis method to confirm the relationship between the quantity and bioactivity of the compounds in each extract. The findings of this study demonstrate the potent therapeutic efficacy of SCS and its potential use as a cost-effective natural alternative medicine against type 2 diabetes and its complications.

Bioassay-Guided Isolated Compounds from Morinda officinalis Inhibit Alzheimer's Disease Pathologies.

Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer's disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease, M. officinalis has not been evaluated in an AD bioassay. Therefore, M. officinalis extracts and fractions were tested for AD-related activity, including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), and advanced glycation end-product (AGE) formation. A bioassay-guided approach led to isolation of 10 active compounds, eight anthraquinones (1-8), one coumarin (9), and one phytosterol (10), from n-hexane and ethyl acetate fractions of M. officinalis. The five anthraquinones (4-8) were stronger inhibitors of AChE than were other compounds. Compounds 3 and 9 were good inhibitors of BChE, and compounds 3 and 8 were good inhibitors of BACE1. Compounds 1-5 and 7-9 were more active than the positive control in inhibiting AGE formation. In addition, we first suggested a structure-activity relationship by which anthraquinones inhibit AChE and BACE1. Our findings demonstrate the preventive and therapeutic efficacy of M. officinalis for AD and its potential use as a natural alternative medicine.

Quantitative determination of 15 bioactive triterpenoid saponins in different parts of Acanthopanax henryi by HPLC with charged aerosol detection and confirmation by LC-ESI-TOF-MS.

Triterpenoid saponins are difficult to analyze using high-performance liquid chromatography coupled to UV/vis spectrophotometry due to their lack of chromophores. This study describes the first analytical method for the determination of 15 triterpenoid saponins from the leaves, stems, root bark, and fruits of Acanthopanax henryi, using a high-performance liquid chromatography with charged aerosol detection coupled with electrospray ionization mass spectrometry method. The separation was carried out on a Kinetex XB-C18 column with an acetonitrile/water gradient as the mobile phase, followed by charged aerosol detection. The operating conditions of charged aerosol detection were set at 24 kPa for nitrogen pressure and 100 pA for the detection range. Liquid chromatography with electrospray ionization mass spectrometry is described for the identification of compounds in plant samples. The electrospray ionization mass spectrometry method involved the use of the [M + Na](+) and [M + NH4 ](+) ions for compounds 1-15 in the positive ion mode with an extracted ion chromatogram. The developed method was fully validated in terms of linearity, sensitivity, precision, repeatability, and recovery, then subsequently applied to evaluate the quality of A. henryi.

Scopoletin from Cirsium setidens Increases Melanin Synthesis via CREB Phosphorylation in B16F10 Cells.

In this study, we isolated scopoletin from Cirsium setidens Nakai (Compositae) and tested its effects on melanogenesis. Scopoletin was not toxic to cells at concentrations less than 50 µM and increased melanin synthesis in a dose-dependent manner. As melanin synthesis increased, scopoletin stimulated the total tyrosinase activity, the rate-limiting enzyme of melanogenesis. In a cell-free system, however, scopoletin did not increase tyrosinase activity, indicating that scopoletin is not a direct activator of tyrosinase. Furthermore, Western blot analysis showed that scopoletin stimulated the production of microphthalmia-associated transcription factor (MITF) and tyrosinase expression via cAMP response element-binding protein (CREB) phosphorylation in a dose-dependent manner. Based on these results, preclinical and clinical studies are needed to assess the use of scopoletin for the treatment of vitiligo.

Effects of caffeoylquinic acid analogs derived from aerial parts of Artemisia iwayomogi on adipogenesis.

Artemisia iwayomogi (AI) is a perennial herb found in Korea. Its ground parts are dried and used in food and traditional medicine for treating hepatitis, inflammation, cholelithiasis, and jaundice. In this study, the anti-obesity effects of single compounds isolated from AI extracts on adipose tissue were investigated. Results demonstrated that caffeoylquinic acid analogs strongly inhibited adipocyte differentiation from 3T3-L1 preadipocytes and reduced neutral lipids in differentiated adipocytes. Accordingly, lipid accumulation in adipocytes decreased, and lipid droplets became granulated. Caffeoylquinic acid analogs suppressed the expression of adipocyte differentiation marker genes, namely, Cebpa, Lep, and Fabp4, but it induced the expression of Ucp1, Ppargc1a, and Fgf21, which are browning biomarkers. Therefore, caffeoylquinic acid analogs from AI inhibited preadipocyte differentiation and induced adipose tissue browning, suggesting that these compounds could be promising therapeutic agents for obesity.

Protective effect of extract from Rumex aquaticus herba on ethanol-induced gastric damage in rats.

BACKGROUND/AIMS: In this study, we investigated the gastroprotective effect of extract including quercetin-3-O-ß-D-glucuronopyranoside (EIQ) from Rumex aquaticus herba against the ethanol-induced gastric damage in rats. METHODS: The rats were divided into eight groups composed of a non-ethanol group, only EIQ (10 mg/kg) group, groups with absolute ethanol after pretreatment with various doses of EIQ (1, 3 and 10 mg/kg), rebamipide (10 mg/kg), stillen (40 mg/kg) and a control receiving only absolute ethanol. Ethanol-induced gastric lesions, lipid peroxidation, neutrophil infiltration and glutathione level were measured. Superoxide dismutase (SOD) and catalase activity were assessed by an assay kit. Protein expression of SOD, catalase or hemoxygenase-1 (HO-1) was assessed by western blotting analysis. RESULTS AND CONCLUSION: In the absolute ethanol treated group, gastric lesion and malondialdehyde levels were significantly increased with enhanced myeloperoxidase activity. Administration of EIQ 1 h prior to ethanol treatment significantly inhibited the formation of gastric lesions and the elevation of the malondialdehyde levels with myeloperoxidase activity. In addition, pretreatment with EIQ significantly increased the level of glutathione, and elevated the activity and protein expression of radical scavenging enzymes, such as SOD, catalase and HO-1. EIQ may exert anti-inflammatory and anti-oxidative effects against ethanol-induced gastric injury through the reduction of lipid peroxidation, myeloperoxidase activity and free radicals.

YES-10 Improves Stress, Tension, and Fatigue by Reducing Cortisol and IL-6 Levels.

The extract of Clematis mandshurica Rupr. (CMR) inhibits the production of proinflammatory mediators from lipopolysaccharide-stimulated peritoneal macrophages and concanavalin A-stimulated splenocytes. Erigeron annuus Pers. (EAP) extract suppresses the production of reactive oxygen species (ROS) from preadipocytes. Furthermore, the mixture of the leaf extracts of CMR and EAP, YES-10®, protected against nerve injuries induced by ischemia/reperfusion, suggesting a ROS-scavenging action. These observations show the anti-inflammatory action of YES-10. Inflammatory cytokines can cause alterations in mental function, including depression, by influencing the neurotransmitter system. Thus, it was hypothesized that YES-10 could improve mental health, such as depression, anxiety, and sense of well-being. Seventy-two subjects were recruited and randomly divided into YES-10 or placebo groups (n = 36 per group). Each group was daily administered two capsules orally, containing 200 mg of YES-10 or placebo, for 4 weeks in a double-blinded manner and tested for levels of depression, anxiety, well-being, and mental fitness using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychosocial Well-being Index (PWI), and Mental Fitness Scale (MFS). In addition, the levels of cortisol (a stress hormone), interleukin-6 (IL-6) (an inflammatory cytokine), and 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative stress) in the serum were measured. The BDI, BAI, PWI, and MFS scores decreased significantly, and the serum levels of cortisol, IL-6, and 8-OHdG were lowered significantly (P < .05), suggesting that YES-10 has the ability to improve mental health by relieving stress and by decreasing inflammation and oxidative stress.

A Complex of Cirsium japonicum var. maackii (Maxim.) Matisum. and Thymus vulgaris L. Improves Menopausal Symptoms and Supports Healthy Aging in Women.

We evaluated the efficacy and safety of MS-10® for the treatment of menopausal symptoms. A double-blind randomized placebo-controlled clinical trial was performed in 71 premenopausal women for 4 and 12 weeks. A total of 12 individual menopausal symptom scores were assessed using the Kupperman index. MS-10 treatment effectively improved the symptoms by ∼48%. In addition, the quality of life of the women improved by 36% from four perspectives: vasomotor, psychosocial, physical, and sexual symptoms as evaluated using the menopause-specific quality of life (MenQoL) questionnaire. Our results show that MS-10 improves insulin-like growth factor-1 (IGF-1) and estrogen utilization through receptor activation, which are thought to have causative therapeutic effects on menopause and aging inhibition in women. Improvement of Enthotheline-1 (ET-1) in the blood after MS-10 intake led to an improvement in menopausal vascular symptoms. Improvements in bone formation and absorption markers such as osteocalcin, bone-specific alkaline phosphatase (BSALP), C-telopeptides of type I collagen (CTx), deoxypyridinoline (deoxyPYD), and N-telopeptides of type I collagen (NTx) in blood or urine indicate that MS-10 fundamentally improves bone health in women. By confirming the improvement of the psychological well-being index based on the improvement of stress hormone cortisol, MS-10 can solve causative psychological and physical stress-related symptoms. Moreover, various safety tests, such as those for female hormones, were confirmed. Therefore, it can be confirmed that MS-10 is a natural pharmaconutraceutical that causatively and safely improves health of women and aids in antiaging processes.

Parishin C attenuates phencyclidine-induced schizophrenia-like psychosis in mice: involvements of 5-HT1A receptor.

Parishin C, a major component of Gastrodia elata BLUME (GE), was purified from GE. Because GE modulates the serotonergic system and the 5-HT(1A) receptor is an important therapeutic target of schizophrenia, we examined whether parishin C affects phencyclidine-induced abnormal behaviors in mice. Phencyclidine-induced abnormal behaviors were significantly ameliorated by parishin C. These effects were reversed by WAY 100635, a 5HT(1A)-receptor antagonist. Consistently, parishin C showed high affinity at 5-HT(1A) receptor as well as a 5-HT(1A)-agonist activity in a 8-OH-DPAT-stimulated [(35)S]GTP-gammaS binding assay. Our results suggest that the antipsychotic effects of parishin C require activation of 5-HT(1A) receptors.

Cynandione A from Cynanchum wilfordii inhibits hepatic de novo lipogenesis by activating the LKB1/AMPK pathway in HepG2 cells.

Cynandione A (CA), isolated from ethyl acetate extract of Cynanchum wilfordii (CW), is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases. Hepatic de novo lipogenesis is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is thought to be a hepatic manifestation of certain metabolic syndromes. However, it has not yet been reported if CA has any therapeutic value in these diseases. Here, we investigated whether CA can inhibit hepatic lipogenesis induced by liver X receptor α (LXRα) using an in vitro model. We found that the extract and ethyl acetated layer of CW decreased the mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c), which plays a crucial role in hepatic lipogenesis. Additionally, we observed that CA could suppress the level of SREBP-1c, which was increased using two commercial LXRα agonists, GW3954 and T0901317. Moreover, the enzymes that act downstream of SREBP-1c were also inhibited by CA treatment. To understand the mechanism underlying this effect, the levels of phosphorylated AMP kinase (pAMPK) were measured after CA treatment. Therefore, CA might increase the pAMPK level by inducing phosphorylation of liver kinase B1 (LKB1), which can then convert AMPK to pAMPK. Taken together, we conclude that CA has an alleviative effect on hepatic lipogenesis through the stimulation of the LKB1/AMPK pathway.

Anti­inflammatory role of Prunus persica L. Batsch methanol extract on lipopolysaccharide­stimulated glial cells.

Glial cells are the resident immune cells of the central nervous system. Reactive glial cells release inflammatory mediators that induce neurotoxicity or aggravate neurodegeneration. Regulation of glial activation is crucial for the initiation and progression of neuropathological conditions. Constituents of the peach tree (Prunus persica L. Batsch), which has a global distribution, have been found to exert therapeutic effects in pathological conditions, such as rashes, eczema and allergies. However, the therapeutic potential of its aerial parts (leaves, fruits and twigs) remains to be elucidated. The present study aimed to evaluate the anti­inflammatory role of P. persica methanol extract (PPB) on lipopolysaccharide (LPS)­stimulated glial cells. High­performance liquid chromatography coupled with tandem mass spectrometry analysis showed that PPB contained chlorogenic acid and catechin, which have antioxidant properties. Western blot and reverse transcription polymerase chain reaction results indicated that PPB reduced the transcription of various proinflammatory enzymes (nitric oxide synthase and cyclooxygenase­2) and cytokines [tumor necrosis factor­α, interleukin (IL)­1ß and IL­6] in LPS­stimulated BV2 cells. In addition, PPB inhibited the activation of NF­κB and various mitogen­activated protein kinases required for proinflammatory mediator transcription. Finally, nitrite measurement and immunocytochemistry results indicated that PPB also suppressed nitrite production and NF­κB translocation in LPS­stimulated primary astrocytes. Thus, PPB may be used as a potential therapeutic agent for neurodegenerative diseases and neurotoxicity via the suppression of glial cell activation.

Regulation of adiponectin receptor 2 expression via PPAR-alpha in NIT-1 cells.

Adiponectin receptors mediate the antidiabetic effects of adiponectin. Although suggested to be mainly expressed in muscle, liver, and adipocyte cells, the expression of adiponectin receptors in beta cells is unclear. Given the primary involvement of this cell type in diabetes mellitus, we presently examined the expression level of adiponectin receptor 2 (AdiR2) in beta cells. Expression was significantly increased under acute hyperlipidemic conditions but impaired under chronic conditions. The impaired AdiR2 expression may play a role in worsened beta cell function. Clofibrate, an agonist of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) delayed the palmitate-induced impairment of AdiR2 expression and PPAR-alpha; this delay was abolished by PPAR-alpha targeted small interfering RNA. The results suggest that AdiR2 expression is regulated by palmitate via PPAR-alpha.

Anti-inflammatory phenylpropanoid glycosides from Clerodendron trichotomum leaves.

The chromatographic separation of MeOH extract from Clerodendron trichotomum Thunberg leaves led to the isolation of three phenylpropanoid compounds. Using spectroscopic methods, the structures of these compounds were determined as beta-(3', 4'-dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(4-O-caffeoyl)-glucopyranoside, acteoside (verbascoside) (1), beta-(3', 4'-dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(6-O-caffeoyl)-glucopyranoside, isoacteoside (2), beta-(3', 4'-dihydroxyphenyl) ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-glucopyranoside, and decaffeoylacteoside (3). We measured the anti-inflammatory activity of these three phenylpropanoid compounds both in vitro (DPPH reduction assay, TBARS assay on Cu (2+)-induced oxidized LDL, PGE(2) assay) and in vivo (acetic acid induced vascular permeability in mice and carrageenan-induced hind paw edema in rats). 80% methanol fraction and acteoside had the activity.