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Background: The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages., Methods: MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund's Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis., Results: MOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1β, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages., Conclusion: MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.

Ethnopharmacological Relevance: Osteoporosis is a chronic epidemic which can leads to enhanced bone fragility and consequent an increase in fracture risk. Traditional Chinese medicine (TCM) formulas have a long history of use in the prevention and treatment of osteoporosis. Antiosteoporotic TCM formulas have conspicuous advantage over single drugs. Systematic data mining of the existing antiosteoporotic TCM formulas database can certainly help the drug discovery processes and help the identification of safe candidates with synergistic formulations. In this review, the authors summarize the clinical use and animal experiments of TCM formulas and their mechanism of action, and discuss the potential antiosteoporotic activity and the active constituents of commonly used herbs in TCM formulas for the therapy of osteoporosis., Materials and Methods: The literature was searched from Medline, Pubmed, ScienceDirect, Spring Link, Web of Science, CNKI and VIP database from 1989 to 2015, and also collected from Chinese traditional books and Chinese Pharmacopoeia with key words such as osteoporosis, osteoblast, osteoclast, traditional Chinese medicine formulas to identify studies on the antiosteoporotic effects of TCM formulas, herbs and chemical constituents, and also their possible mechanisms., Results: Thirty-three TCM formulas were commonly used to treat osteoporosis, and showed significant antiosteoporotic effects in human and animal. The herb medicines and their chemical constituents in TCM formulas were summarized, the pharmacological effects and chemical constituents of commonly used herbs in TCM formulas were described in detail. The action mechanisms of TCM formulas and their chemical constituents were described. Finally, the implication for the discovery of antiosteoporotic leads and combinatory ingredients from TCM formulas were prospectively discussed., Conclusions: Clinical practice and animal experiments indicate that TCM formulas provide a definite therapeutic effect on osteoporosis. The active constituents in TCM formulas are diverse in chemical structure, and include flavonoids, lignans, saponins and iridoid glycosides. Antiosteoporotic mechanism of TCM formulas and herbs involves multi regulatory pathways, such as Wnt/β-catenin, BMP/Smad, MAPK pathway and RANKL/OPG system. Phytochemicals from TCM formulas and their compositional herb medicines offer great potential for the development of novel antiosteoporotic drugs. The active ingredients in TCM formulas can be developed in combination as potent drugs, which may exhibit better antiosteoporotic effects compared to the individual compound., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Context: Portulacerebroside A (PCA) is a novel cerebroside compound isolated from Portulaca oleracea L. (Portulacaceae), an edible and medicinal plant distributed in the temperate and tropical zones worldwide., Objective: This study investigates the effects of PCA in human liver cancer HCCLM3 cells on metastasis and invasion., Materials and Methods: After the cells were treated with PCA (2.5, 5, and 10 μg/ml) for 6, 12, 24, or 48 h, adhesion, transwell invasion, and scratch tests were conducted and cell functions were evaluated. Western blot and FQ-RT-PCR assays explored the mechanism of PCA-inhibited invasion and metastasis in the cells., Results: The adhesion rate of the cells was suppressed at 0.5 h (79.4 ± 1.0, 68.7 ± 1.3, and 58.1 ± 1.3%, versus 100 ± 1.5% in the control), 1 h (78.2 ± 1.2, 70.9 ± 1.6, and 55.4 ± 1.9%, versus 100 ± 1.2% in the control), and 1.5 h (71.6 ± 1.1, 62.3 ± 0.9, and 50.4 ± 0.9%, versus 100 ± 1.1% in the control). The 24 h invasion ability was decreased (356.6 ± 11.2, 204.0 ± 17.6, and 113.0 ± 9.5%, versus 443.6 ± 15.4% in the control). The migration capability was also restrained by PCA for 24 h (324.8 ± 25.4, 250.4 ± 21.0, and 126.3 ± 10.1, versus 381.6 ± 30.6 in the control) and 48 h (470.3 ± 34.3, 404.0 ± 19.7, and 201.0 ± 15.4, versus 752.0 ± 63.6 in the control). There was an increase in the mRNA and protein expression levels of TIMP-2 and nm23-H1, inhibition in the mRNA expression of MTA1, MMP-2, and MMP-9, and suppression in the protein expression of MTA1, RhoA, Rac1/Cdc42, MMP-2, but not RhoC and MMP-9., Conclusion: PCA suppresses the invasion and metastasis of HCCLM3 cells possibly by modulation of the mRNA and protein expression of related parameters. This is the first study to reveal a new potential therapeutic application of PCA in antimetastatic therapy for liver cancer.

Portulaca oleracea L., belonging to the Portulacaceae family, is commonly known as purslane in English and Ma-Chi-Xian in Chinese. It is a warm-climate, herbaceous succulent annual plant with a cosmopolitan distribution. It is eaten extensively as a potherb and added in soups and salads around the Mediterranean and tropical Asian countries and has been used as a folk medicine in many countries. Diverse compounds have been isolated from Portulaca oleracea, such as flavonoids, alkaloids, polysaccharides, fatty acids, terpenoids, sterols, proteins vitamins and minerals. Portulaca oleracea possesses a wide spectrum of pharmacological properties such as neuroprotective, antimicrobial, antidiabetic, antioxidant, anti-inflammatory, antiulcerogenic, and anticancer activities. However, few molecular mechanisms of action are known. This review provides a summary of phytochemistry and pharmacological effects of this plant.

A highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of actinoside E in rat plasma. The analytes were extracted by ethyl acetate and an analogue of actinoside F was used as the internal standard. The mobile phase consisted of methanol-water (50: 50, V/V) containing 0.1% formic acid was delivered at a flow rate of 0.3 mL·min(-1) to a Zorbax SB-C18 column (100 mm × 2.1 mm, 3.5 μm). The detection was performed by electrospray ionization mass spectrometry in the negative multiple reaction monitoring mode with a chromatograph run time of 3.0 min. Calibration curves of actinoside E were linear in the range of 0.5-2 500 ng·mL(-1). In this range, intra- and inter-day precision ranged from 1.7% to 7.5% and 2.0% to 8.9%, respectively. The accuracy ranged from 95.7% to 108.6%, and extraction recovery from 83.2% to 85.5%. This method was successfully applied to a pharmacokinetic study of actinoside E in rats after intravenous (5 mg·kg(-1)) and oral (100 mg·kg(-1)) administration, and the results showed that actinoside E was poorly absorbed with an absolute bioavailability being approximately 0.27%., (Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Two new triterpenoids, 30-O-beta-D-glucopyranosyloxy-2alpha,3alpha,24-trihydroxyurs-12,18-diene-28-oic acid O-beta-D-glucopyranosyl ester (1) and 2alpha,3beta,3,30-tetrahydroxyurs-12,18-diene-28-oic acid O-beta-D-glucopyranosyl ester (2) were isolated from roots of Actinidia valvata Dunn. Their structures were elucidated by means of extensive spectroscopic studies. Both these two new compounds showed moderate cytotoxic activity in vitro against BEL-7402 and SMMC-7721 tumor cell line.

The present study was undertaken to investigate the anti-inflammatory and analgesic activity of total flavone of branches and leaves of Cunninghamia lanceolata (TFC) to provide a scientific basis for its clinical use and resource development. TFC was evaluated for anti-inflammatory and analgesic activity in mice or rats using chemical and thermal models of nociception, including acetic acid-induced writhing test, hot plate latency test, formalin test and carrageenan induced paw oedema test. Results showed that TFC given orally can significantly attenuate acetic acid-induced writhing in mice in a dose-dependent manner. In the hot plate latency test, TFC showed common activity in prolonging duration time only at the highest dose (400 mg/kg). Each dose of TFC could not significantly inhibit the first phase but was active in the later phase of formalin-induced pain, whereas morphine showed notable activity in the two phases. In the carrageenan-induced paw oedema model, TFC could significantly and dose-dependently reduce the carrageenan-induced paw edema at the third and fifth hour, and decrease the content of PEG(2) in paw edema tissue and that of COX-2 in blood serum. It may be concluded that TFC showed both anti-inflammatory and analgesic effects, showing that it can be of importance in drug development, especially in the field of pain and inflammation.

Aim of the Study: To investigate the effects of the ethanol extract from Portulaca oleracea (EEPO) on hypoxia models mice and to find the possible mechanism of its anti-hypoxic actions so as to elucidate the anti-hypoxia activity and provide scientific basis for the clinical use of Portulaca oleracea., Materials and Methods: EEPO was evaluated on anti-hypoxic activity in several hypoxia mice models, including closed normobaric hypoxia and sodium nitrite or potassium cyanide toxicosis. To verify the possible mechanism(s), we detected the activities of pyruvate kinase (PK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and the level of adenosine triphosphate (ATP) in mice cortices., Results: Given orally, the EEPO at doses of 100, 200, 400 mg/kg could dose-dependently enhance the survival time of mice in both of the normobaric and chemical hypoxia models. The activity of the glycolysis enzymes and the level of ATP were higher than those of the control. In the pentobarbital sodium-induced sleeping time test and the open-field test, EEPO neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-hypoxic activity was unlikely due to sedation or motor abnormality., Conclusions: These results demonstrated that the EEPO possessed notable anti-hypoxic activity, which might be related to promoting the activity of the key enzymes in glycolysis and improving the level of ATP in hypoxic mice.

The ethanol extract of the fruits of Vitex rotundifolia (VRE) and its four major compounds (casticin, luteolin, rotundifuran and agnuside) were tested for their estrogen-like activity by using the modified cell proliferation assay (E-SCREEN assessment system), as well as the estrogen receptor (ER(alpha)), estrogen receptor-regulated progesterone receptor and pS2 mRNA expression in MCF-7 cells. The results showed that only agnuside and rotundifuran could stimulate the proliferation of MCF-7 cells. These actions were dose dependent (range from 100 nM to 10 microM) and could be significantly inhibited by the specific estrogen receptor antagonist ICI 182,780. The estrogen receptor ER(alpha) and the estrogen receptor-regulated progesterone receptor and pS2 mRNA levels were increased by treatment with rotundifuran and agnuside within 24 h, and the effects could be reversed by ICI 182,780. The standardization of the extract and constituents were carried out by means of a high-performance liquid chromatography-fingerprint. It was concluded that VRE and its compounds showed estrogen-like activity and that the estrogenic effects of rotundifuran and agnuside were mediated by the estrogen inducible gene, which may be useful in regulating the hormone levels to treat related diseases. However, further studies are required to assess the physiological significance of VRE in animals and man.

Objective: To systematically evaluate the protective effects of Humulus lupulus L. extract (HLE) on osteoporosis mice. Methods: In vivo experiment, a total of 35 12-week-old female ICR mice were equally divided into 5 groups: the sham control group (sham); the ovariectomy with vehicle group (OVX); the OVX with estradiol valerate [EV, 0.2 mg/(kg•d)] the OVX with low- or high-dose HLE groups [HLE, 1 g/(kg•d) and 3 g/(kg•d)], 7 in each group. Treatment began 1 week after the ovariectomized surgery and lasted for 12 weeks. Bone mass and trabecular bone mircoarchitecture were evaluated by micro computed tomography, and bone turnover markers in serum were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. In vitro experiment, osteoblasts and osteoclasts were treated with HLE at doses of 0, 4, 20 and 100 µg/mL. Biomarkers for bone formation in osteoblasts and bone resorption in osteoclasts were analyzed. Results: Compared with the OVX group, HLE exerted bone protective effects by the increase of estradiol (P<0.05), the improvement of cancellous bone structure, bone mineral density (P<0.01) and the reduction of serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), bone gla-protein, c-terminal telopeptides of type I collagen (CTX-I) and deoxypyridinoline levels (P<0.01 for all). In vitro experiment, compared with the control group, HLE at 20 µg/mL promoted the cell proliferation (P<0.01), and increased the expression of bone morphogenetic protein-2 and osteopontin levels in osteoblasts (both P<0.05). HLE at 100 µg/mL increased the osteoblastic ALP activities, and HLE at all dose enhanced the extracellular matrix mineralization (both P<0.01). Furthermore, compared with the control group, HLE at 20 µg/mL and 100 µg/mL inhibited osteoclastic TRAP activity (P<0.01), and reduced the expression of matrix metalloproteinase-9 and cathepsin K (both P<0.05). Conclusion: HLE may protect against bone loss, and have potentials in the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. Methods: An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods. Results: Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus. Conclusion: The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root. [ABSTRACT FROM AUTHOR]