HPLC-PDA Method for Quantification of Bioactive Compounds in Crude Extract and Fractions of Aucklandia costus Falc. and Cytotoxicity Studies against Cancer Cells.

Aucklandia costus Falc. (Synonym: Saussurea costus (Falc.) Lipsch.) is a perennial herb of the family Asteraceae. The dried rhizome is an essential herb in the traditional systems of medicine in India, China and Tibet. The important pharmacological activities reported for Aucklandia costus are anticancer, hepatoprotective, antiulcer, antimicrobial, antiparasitic, antioxidant, anti-inflammatory and anti-fatigue activities. The objective of this study was the isolation and quantification of four marker compounds in the crude extract and different fractions of A. costus and the evaluation of the anticancer activity of the crude extract and its different fractions. The four marker compounds isolated from A. costus include dehydrocostus lactone, costunolide, syringin and 5-hydroxymethyl-2-furaldehyde. These four compounds were used as standard compounds for quantification. The chromatographic data showed good resolution and excellent linearity (r2 ˃ 0.993). The validation parameters, such as inter- and intraday precision (RSD < 1.96%) and analyte recovery (97.52-110.20%; RSD < 2.00%),revealed the high sensitivity and reliability of the developed HPLC method. The compounds dehydrocostus lactone and costunolide were concentrated in the hexane fraction (222.08 and 65.07 µg/mg, respectively) and chloroform fraction (99.02 and 30.21 µg/mg, respectively), while the n-butanol fraction is a rich source of syringin (37.91 µg/mg) and 5-hydroxymethyl-2-furaldehyde (7.94 µg/mg). Further, the SRB assay was performed for the evaluation of anticancer activity using lung, colon, breast and prostate cancer cell lines. The hexane and chloroform fractions show excellent IC50 values of 3.37 ± 0.14 and 7.527 ± 0.18 µg/mL, respectively, against the prostate cancer cell line (PC-3).

Isolation, Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Polygala inexpectata Pesmen & Erik.

Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3'-disinapoyl-sucrose (1), 6-O-sinapoyl,3'-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3'-O-(O-methyl-feruloyl)-sucrose (3), 3'-O-(sinapoyl)-sucrose (4), 3'-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3'-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4'-di-O-methylquercetin-3-O-ß-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities.

Chinese patent medicine Aidi injection for cancer care: An overview of systematic reviews and meta-analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection is one of the China Food and Drug Administration approved Chinese herbal injections and the most competitive product in cancer care in China. It is composed of the extracts from Mylabris Phalerata, Astragalus Membranaceus, Panax Ginseng, and Acanthopanax Senticosus. AIM OF THE STUDY: This overview aims to map systematic reviews (SRs) of Aidi injection for cancer and provide a summarized evidence for clinical practice and decision making. MATERIALS AND METHODS: Seven databases were searched for SRs and/or meta-analyses of randomized controlled trials on Aidi injection for cancer care until December 2020. Six authors worked in pairs independently identified studies, collected data, and assessed the quality of included studies according to the revised Assessment of Multiple Systematic Reviews (AMSTAR 2) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A narrative synthesis was used for the evidence mapping. RESULTS: Fifty-two SRs on Aidi injection as adjuvant therapy were included, involving lung cancer (20 SRs), liver cancer (10), colorectal cancer (7), gastric cancer (6), lymphoma (2), breast cancer (2), esophageal cancer (1), ovary cancer (1), and a mix of different cancers (4). Except for one SR focusing on Aidi injection used alone, other SRs evaluated Aidi injection in combination with chemotherapy (43), radiotherapy (4), or chemo/radiology/targeting therapy (4). Aidi injection showed additional beneficial effects on survival (9), objective response rate (44), quality of life (42), and the reduction of side-effects from chemo/radiotherapy (48). Using AMSTAR 2 tool, two reviews were assessed as low and the rest as critically low methodological quality mainly due to the lack of prospective registration. The reporting quality was insufficient assessed with PRISMA in the reporting of search strategy (26, 50.0%), additional analysis (19, 36.5%), and the summary of evidence (2, 3.8%). CONCLUSION: Aidi injection has been evaluated for its adjuvant beneficial effects on cancer survival, tumor responses, quality of life, and reducing the side effects of chemo/radiotherapy, mainly focusing on lung, liver and colorectal cancer. The methodological and reporting quality are weak and need to be improved in the future.

Exploring the resources of the genus Viscum for potential therapeutic applications.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Viscum comprises approximately 100 species that are mainly distributed across Africa, Asia and Europe. The extracts and preparations of Viscum species are widely used as common complementary and alternative medicines in the treatment of rheumatism and cancer. AIM OF THE REVIEW: This review aims to explore the medicinal properties of twelve species belonging to the genus Viscum for potential therapeutic applications. MATERIALS AND METHODS: We collected online information (including PubMed, CNKI, Google Scholar, and Web of Science) from January 1915 to April 2021 and knowledge from classical books on Chinese herbal medicines available for 12 species of the genus Viscum, including Viscum coloratum (Kom.) Nakai, Viscum album L., Viscum articulatum Burm. f., Viscum liquidambaricola Hayata, Viscum ovalifolium DC., Viscum capitellatum Sm., Viscum cruciatum Sieber ex Boiss., Viscum nudum Danser, Viscum angulatum B.Heyne ex DC., Viscum tuberculatum A.Rich., Viscum multinerve Hayata, and Viscum diospyrosicola Hayata. RESULTS: At least 250 different compounds have been reported across twelve Viscum species, including amino acid and peptides, alkaloids, phenolic acids, flavonoids, terpenoids, carbohydrates, fatty acids, lipids, and other types of compounds. In particular, for Viscum coloratum (Kom.) Nakai and Viscum album L., the plants, preparations, and bioactive components have been thoroughly reviewed. This has allowed to elucidate the role of active components, including lectins, viscotoxins, flavonoids, terpenoids, phenolic acids, and polysaccharides, in multiple bioactivities, such as anti-cancer, anti-rheumatism arthralgia, anti-inflammation, anti-cardiovascular diseases, enhancing immunity, and anti-chemotherapy side effects. We also evaluated quality control methods based on active compounds, in vivo exposure compounds, and discriminated chemical markers. CONCLUSIONS: This is the first report to systematically review the pharmaceutical development history, chemical composition, clinical evidence, pharmacological activity, discriminated chemical markers, in vivo exposure, and quality control on twelve distinct species of Viscum plants with medicinal properties. The significant safety and efficacy, along with the minor side effects are constantly confirmed in clinics. The genus Viscum is thus an important medicinal resource that is worth exploring and developing in future pharmacological and chemical studies.

Syringin: A Phenylpropanoid Glycoside Compound in Cirsium brevicaule A. GRAY Root Modulates Adipogenesis.

Cirsium brevicaule A. GRAY is a wild perennial herb, and its roots (CbR) have traditionally been used as both food and medicine on the Japanese islands of Okinawa and Amami. The present study evaluated the antiadipogenic effect of CbR using mouse embryonic fibroblast cell line 3T3-L1 from JCRB cell bank. Dried CbR powder was serially extracted with solvents of various polarities, and these crude extracts were tested for antiadipogenic activity. Treatment with the methanol extract of CbR showed a significant suppression of lipid accumulation in 3T3-L1 cells. Methanol extract of CbR was then fractionated and subjected to further activity analyses. The phenylpropanoid glycosidic molecule syringin was identified as an active compound. Syringin dose dependently suppressed lipid accumulation of 3T3-L1 cells without cytotoxicity, and significantly reduced the expressions of peroxisome proliferator-activated receptor gamma, the master regulator of adipogenesis, and other differentiation markers. It was demonstrated that syringin effectively enhanced the phosphorylation of the AMP-activated protein kinase and acetyl-CoA carboxylase. These results indicate that syringin attenuates adipocyte differentiation, adipogenesis, and promotes lipid metabolism; thus, syringin may potentially serve as a therapeutic candidate for treatment of obesity.

A hybrid platform featuring nanomagnetic ligand fishing for discovering COX-2 selective inhibitors from aerial part of Saussurea laniceps Hand.-Mazz.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea laniceps Hand.-Mazz. (Compositae) is a representative "snow lotus" herb well known in Chinese folk medicine to treat inflammation-related diseases such as arthritis. S. laniceps (SL) shows anti-inflammatory and analgesic potencies and contains various constituents potentially with cyclooxygenase-2 (COX-2) selective inhibition. The herb is a valuable source of natural alternatives to synthetic COX-2 selective nonsteroidal anti-inflammatory drugs, a common medication for rheumatoid arthritis (RA) and osteoarthritis (OA) reported with serious cardiovascular side effects. AIM OF THE STUDY: Based on an innovative drug screening platform, this study aimed to discover safe, effective COX-2 selective inhibitors from SL. MATERIALS AND METHODS: An enzyme-anchored nanomagnetic fishing assay was developed to separate COX-2 ligands from SL. Cell and animal models of cardiomyocytes, lipopolysaccharide-stimulated macrophages, rat adjuvant-induced arthritis, and anterior cruciate ligament transection-induced OA rats, were adopted to screen the single/combined ligands regarding toxicity and bioactivity levels. Molecular docking was employed to unravel binding mechanisms of the ligands towards COX-1 and COX-2. RESULTS: Four COX-2 selective compounds were separated from SL using optimized COX-2-functionalized magnetic nanoparticles. All the four ligands were proved with evidently lower cardiotoxicity both in vitro and in vivo than celecoxib, a known COX-2 selective inhibitor. Two ligands, scopoletin and syringin, exhibited potent anti-arthritic activities in rat models of RA and OA by alleviating clinical statuses, immune responses, and joint pathological features; their optimum combination ratio was discovered with stronger remedial effects on rat OA than single administrations. The COX-1/2 binding modes of the two phytochemicals contributed to explain their cardiac safety and therapeutic performances. CONCLUSIONS: The screened chemicals are promising to be developed as COX-2 selective inhibitors as part of treating RA and OA. The hybrid strategy for discovering therapeutic agents from SL is shown here to be efficient; it should be equally valuable for finding other active chemicals in other natural sources.

Syringin alleviates ovalbumin-induced lung inflammation in BALB/c mice asthma model via NF-κB signaling pathway.

Asthma is an allergic chronic inflammatory disease of the pulmonary airways, characterized by the infiltration of white blood cells and release of inflammatory cytokines of complex pathways linked to its pathogenesis. Syringin extracted from various medicinal plants has been used extensively for the treatment of inflammatory diseases. Hence, this study was conducted to further explore the protective effects of the syringin in ovalbumin (OVA) induced-asthma mice model. OVA-sensitized BALB mice were treated intraperitonealy with three doses (25, 50 and 100 mg/kg) of the syringin which was validated by the alteration in the immunoglobulin E (IgE) levels, cytokines levels, histopathological evaluation inflammatory cell count, lung weight, nitrite (NO) levels, oxidative stress biomarkers and gene markers. The treatment of syringin intensely reduced the increased IgE, inflammatory cytokines, WBC count and restored the antioxidant stress markers OVA stimulated animals. In addition, a significant reduction in inflammation and mucus production was evidenced in histopathological analysis which was further validated by suppression NF-κB pathway activation by syringin. These results suggest that syringin may improve asthma symptoms in OVA-induced mice by modulating NF-κB pathway activation.

Protective effects of syringin against oxidative stress and inflammation in diabetic pregnant rats via TLR4/MyD88/NF-κB signaling pathway.

Gestational diabetes (GDM) is common in pregnancies due to the inflammation and oxidative stress-mediated insulin resistance. In the present study, GDM was induced in the Wistar rats by administering the streptozotocin to elucidate whether the administration of syringin (50 mg/kg/day) during pregnancy could improve maternal glycemia and protect against the complications of GDM. The animals were assessed for their morphological changes in the ß-islets of Langerhans and their insulin-producing ability, inflammatory cytokine markers, and the involvement of TLR4/MyD88/NF-κB signaling pathway using RT-PCR. The results demonstrated that the onset of GDM demonstrated pancreatic tissue degeneration in the islets of Langerhans with a significant increase in oxidative stress and reduced antioxidant enzymes. Besides, the mRNA expression levels of TLR4, MyD88, NF-Kß p65; NLRP3 mRNA were profoundly increased in GDM rats compared to normal pregnant rats. On the other hand, syringin administered GDM rats abrogated the oxidative stress and attenuated the level of the inflammatory cytokines. Intriguingly, the decrease in TLR4 expression and the downstream molecules of MyD88, NF-κB, and NLRP3 were also observed in syringin administered GDM rats that indicate the insulin secretion stimulatory actions of syringin through the suppression of TLR4 signaling. These novel findings of the study provide evidence that syringin could be a probable candidate to be used in the treatment of gestational diabetes in the future.

Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Murine Macrophage Cells.

OBJECTIVE: To study the anti-inflammatory action and cellular mechanism of Oplopanax elatus. METHODS: A hot water extract of OE (WOE) was prepared and a major constituent, syringin, was successfully isolated. Its content in WOE was found to be 214.0 µg/g dried plant (w/w). Their anti-inflammatory activities were examined using RAW 264.7 macrophages and a mouse model of croton oil-induced ear edema. RESULTS: In lipopolysaccharide (LPS)-treated RAW 264.7 cells, a mouse macrophage cell line, WOE was found to significantly and strongly inhibit cyclooxygenase-2 (COX-2)-induced prostaglandin E2 (PGE2) production [half maximal inhibitory concentration (IC50)=135.2 µg/mL] and inducible nitric oxide synthase (iNOS)-induced NO production (IC50=242.9 µg/mL). In the same condition, WOE was revealed to inhibit NO production by down-regulating iNOS expression, mainly by interrupting mitogen activated protein kinases (MAPKs)/activator protein-1 (AP-1) pathway. The activation of all three major MAPKs, p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was inhibited by WOE (50-300 µg/mL). On the other hand, WOE reduced PGE2 production by inhibiting COX-2 enzyme activity, but did not affect COX-2 expression levels. In addition, WOE inhibited the production of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. In croton oil-induced ear edema in mice, oral administration of WOE (50-300 mg/kg) dose-dependently inhibited edematic inflammation. CONCLUSION: Water extract of OE exhibited multiple anti-inflammatory action mechanisms and may have potential for treating inflammatory disorders.

A review on the immunomodulatory activity of Acanthopanax senticosus and its active components.

Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, the dried root and rhizome or stem of Acanthopanax senticosus, is commonly known as Siberian ginseng or Ciwujia in Chinese. It is used all over the world as an adaptogen to enhance physical and mental performance for the sake of normal physiological functioning of human bodies under stress. In the theory of traditional Chinese medicine, Ciwujia can strengthen the spleen that is an essential organ for immunological response. Its traditional applications include inflammation, fatigue and cancer in which the immune-regulating function is always involved. In this article, the immunomodulatory activities of Ciwujia extracts, fractions and pure compounds were extensively reviewed first. Then, the possibility of upgrading the chemical markers to bioactive markers was explored. Finally, the potency of aqueous extract and ethanol extract in regulating cytokines production from human peripheral blood mononuclear cells was compared. We conclude that although various phytochemicals such as isofraxidin, syringin and eleutheroside E from Ciwujia have been shown to modulate immunological functions, the aqueous extract of Ciwujia as a whole possesses the most potent efficacy. Therefore, aqueous (rather than ethanol) extract of Ciwujia should be used in order to benefit from its immunomodulatory properties.

Reactive oxygen species mediate the chemopreventive effects of syringin in breast cancer cells.

BACKGROUND: Syringin (Syr), a phenylpropanoid glycoside extracted from Eleutherococcus senticosus, possesses various biological properties, including anticancer activities. However, the cytotoxicity effects of Syr on breast cancer have not yet been elucidated. PURPOSE: In this study, we evaluated the anticancer potential of Syr on breast carcinoma and the mechanism involved. STUDY DESIGN/METHODS: Non-tumorigenic (M10), tumorigenic (MCF7) and metastatic (MDA-MB-231) breast cancer cell lines as well as xenograft model were treated with Syr. Proliferation and cell cycle distribution were evaluated using the MTT, the colony formation assay and flow cytometry. The expression levels of cytotoxicity-related proteins were detected by Western blot. RESULTS: Here, we found that colony formation inhibition, cell cycle arrest in the G2/M phase, down-regulation of X-linked inhibitor of apoptosis protein (XIAP), cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3/9 activation were observed in MCF7 and MDA-MB-231 cells treated with Syr. Moreover, pretreatment with a pan-caspase inhibitor (Z-DEVD-FMK) inhibited Syr-induced apoptosis. In addition, treatment with Syr also increased the production of reactive oxygen species (ROS). However, the antioxidant N-acetyl-cysteine (NAC) reversed the ROS levels and rescued the apoptotic changes. Meanwhile, Syr inhibited the growth of breast cancer xenograft models and dramatically decreased tumor volume without any obvious body weight loss in vivo. CONCLUSION: Our findings suggest that Syr induces oxidative stress to suppress the proliferation of breast cancer and thus might be an effective therapeutic agent to treat breast cancer.

Clinical efficacy and safety of Aidi injection plus paclitaxel-based chemotherapy for advanced non-small cell lung cancer: A meta-analysis of 31 randomized controlled trials following the PRISMA guidelines.

ETHNOPHARMACOLOGICAL RELEVANCE: As an important Chinese herb injection, Aidi injection is composed of the extracts from Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. Aidi injection plus paclitaxel-based chemotherapy is often used to in the treatment of non-small cell lung cancer (NSCLC) in China. AIM OF THE STUDY: The objective of this study is to further confirm whether Aidi injection can improve the tumor responses and survivals, and reveal its safety, optimal usage and combination with paclitaxel. MATERIALS AND METHODS: A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All randomized controlled trials (RCTs) concerning the Aidi injection plus paclitaxel-based chemotherapy for NSCLC were selected. Main outcomes were objective response rate (ORR), disease control rate (DCR), survivals, quality of life (QOL) and adverse drug reactions (ADRs). All data were extracted by using a standard data extraction form and synthesized through meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. RESULTS: Thirty-one RCTs involving 2058 patients were included, and most trials had an unclear methodological bias risk. The risk ratio (RR) and 95% confidence intervals (CI) of ORR, DCR, QOL, neutropenia, thrombocytopenia, gastrointestinal toxicity and liver injury were as following: 1.32 (1.20-1.46), 1.14 (1.09-1.20), 1.89 (1.66-2.16), 0.61 (0.51-0.74), 0.62 (0.45-0.87), 0.59 (0.49-0.72) and 0.52 (0.36-0.75). Compared to chemotherapy alone, all differences were statistically significant. Subgroup analysis showed that only with the TP, Aidi injection could increase the ORR and DCR. Treatment with 100 ml, 80 ml or 50 ml/time, and 14 days/2 cycles or 21 days/2-4 cycles, Aidi injection could increase the ORR and DCR, respectively. Sensitivity analysis showed that the results had good robustness. None of the trials reported the overall survivals (OS), progression free survival (PFS). The quality of evidences was moderate. CONCLUSIONS: Current moderate evidence revealed that Aidi injection plus paclitaxel-based chemotherapy, especially TP can significantly improve the clinical efficacy and QOL for patients with stage III/IV NSCLC. Aidi injection can relieve the risk of hematotoxicity, gastrointestinal toxicity and liver injury in patient with NSCLC receiving paclitaxel-based chemotherapy. The optimal usage may be 50 ml/time and 14 days/2 cycles.

The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes macrocephala Koidz. (called Baizhu in China) is a medicinal plant that has long been used as a tonic agent in various ethno-medical systems in East Asia, especially in China, for the treatment of gastrointestinal dysfunction, cancer, osteoporosis, obesity, and fetal irritability. AIM OF THE REVIEW: This review aims to provide a systematic summary on the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of A. macrocephala to explore the future therapeutic potential and scientific potential of this plant. MATERIALS AND METHODS: A literature search was performed on A. macrocephala using scientific databases including Web of Science, Google Scholar, Baidu Scholar, Springer, PubMed, SciFinder, and ScienceDirect. Information was also collected from classic books of Chinese herbal medicine, Ph.D. and M.Sc. dissertations, unpublished materials, and local conference papers on toxicology. Plant taxonomy was confirmed to the database "The Plant List" (www.theplantlist.org). RESULTS: More than 79 chemical compounds have been isolated from A. macrocephala, including sesquiterpenoids, triterpenoids, polyacetylenes, coumarins, phenylpropanoids, flavonoids and flavonoid glycosides, steroids, benzoquinones, and polysaccharides. Crude extracts and pure compounds of A. macrocephala are used to treat gastrointestinal hypofunction, cancer, arthritis, osteoporosis, splenic asthenia, abnormal fetal movement, Alzheimer disease, and obesity. These extracts have various pharmacological effects, including anti-tumor activity, anti-inflammatory activity, anti-aging activity, anti-oxidative activity, anti-osteoporotic activity, neuroprotective activity, and immunomodulatory activity, as well as improving gastrointestinal function and gonadal hormone regulation. CONCLUSIONS: A. macrocephala is a valuable traditional Chinese medicinal herb with multiple pharmacological activities. Pharmacological investigations support the traditional use of A. macrocephala, and may validate the folk medicinal use of A. macrocephala to treat many chronic diseases. The available literature shows that much of the activity of A. macrocephala can be attributed to sesquiterpenoids, polysaccharides and polyacetylenes. However, there is a need to further understand the molecular mechanisms and the structure-function relationship of these constituents, as well as their potential synergistic and antagonistic effects. Further research on the comprehensive evaluation of medicinal quality, the understanding of multi-target network pharmacology of A. macrocephala, as well as its long-term in vivo toxicity and clinical efficacy is recommended.

Syringin prevents bone loss in ovariectomized mice via TRAF6 mediated inhibition of NF-κB and stimulation of PI3K/AKT.

BACKGROUND: Syringin, also called eleutheroside B, is a main bioactive phenolic glycoside in Acanthopanax senticosus (Rupr. et Maxim.) Harms. Based on the "kidney dominates bone" theory of TCM, A. senticosus can strengthen bone and Syringin may be one of the responsibilities. PURPOSE: The objectives of this study were to estimate the osteoporotic activity of Syringin and reveal the possible molecular mechanisms in vivo. METHODS: Sixty female ICR mice were randomly assigned into sham operated group (SHAM, treated with vehicle) and five ovariectomized subgroups (n = 10 each), treated with vehicle as OVX group, estradiol valerate (EV, 1 mg/kg/day) as positive group, and Syringin (10, 20 and 40 mg/kg/day) as low, moderate and high dosage groups. The therapeutic effect of Syringin against osteoporosis was systematically analyzed by determining the bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and serum biochemical parameters, and the molecular mechanism was also evaluated. RESULTS: After three months of orally administrated intervention, Syringin (10, 20 and 40 mg/kg/day) significantly improved the BMD, bone maximum load and trabecular bone microarchitecture in ovariectomized mice, evidenced by the increased bone mineral content, tissue mineral content, tissue mineral density, trabecular thickness and trabecular number, as well as the decreased trabecular separation in OVX mice. Meanwhile, the activities of tartrate-resistant acid phosphatase, deoxypyridinoline and cathepsin K in OVX mice were also inhibited by Syringin, while the increased body weight and decreased uterus weight seemed not influenced by Syringin administration. Concerning the underlying molecular mechanisms, Syringin significantly downregulated the expression of tumor-necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) and receptor activator of nuclear factor kappa B ligand (RANKL) proteins levels, upregulated the expression of osteoprotegerin (OPG), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) levels, suggesting that Syringin prevented bone lost by TRAF6-mediated inhibition of NF-κB and stimulation of PI3K/AKT, and subsequently increasing the OPG/RANKL ratio and inhibiting the osteoclastogenesis, finally promoting bone formation. CONCLUSIONS: All of the data implied Syringin possessed the potent anti-osteoporosis activity on ovariectomized mice, and the underlying molecular mechanism may be related to the NF-κB and PI3K/AKT signaling pathways.

Aidi injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell lung cancer: A meta-analysis of 42 RCTs following the PRISMA guidelines.

ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection is one of the most commonly used Chinese patent medicines for advanced non-small cell lung cancer (NSCLC). It is made from an extraction of Mylabris Phalerata, Radix Astragalus, Radix Ginseng, and Acanthopanax Senticosus. AIM OF THE STUDY: The objective of this study is to evaluate the efficacy and safety of Aidi injection in combination with platinum-based chemotherapy for stage IIIB/IV NSCLC. MATERIALS AND METHODS: A systematic review and meta-analysis were performed following the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Trials were combined using Review Manager 5.3 and Comprehensive Meta-Analysis(CMA) 2.0. Dichotomous data were expressed as risk ratio (RR) and continuous outcomes as weighted mean difference (WMD), with their 95% confidence intervals (CI) respectively. All randomized controlled trials (RCTs) comparing Aidi injection plus platinum-based chemotherapy versus platinum-based chemotherapy, with efficacy and safety outcomes were selected. Disease Control Rate (DCR) was the primary outcome, Objective Response Rate (ORR), survival rate, quality of life (QOL), and toxic effects were the secondary outcomes. RESULTS: 42 RCTs recruiting 4081 patients with stage IIIB/IV NSCLC were included, with overall low-moderate methodological quality. Compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy can increase relative benefit of DCR (RR = 1.13, 95% CI 1.09-1.16, P < 0.00001), ORR (RR = 1.26, 95% CI 1.18-1.36, P < 0.00001), improve 1-, 2-, 3-year survival rates (RR = 1.14, 95% CI 1.02-1.28, P = 0.03; RR = 1.31, 95% CI 1.05-1.64, P = 0.02; and RR = 1.88, 95% CI 1.32-2.67, P = 0.0005, respectively), QOL (RR = 1.80, 95% CI 1.61-2.01, P < 0.00001), and reduce severe (grade 3 and 4) toxicities by 36% (RR = 0.64, 95% CI 0.58-0.70, P < 0.00001). CONCLUSIONS: From the available evidence, compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy improves the clinical efficacy and alleviates the toxicity of chemotherapy in patients with stage IIIB/IV NSCLC. However, considering the intrinsic limitations of the included RCTs, well-designed, rigorously performed, high-quality trials are still required to further assess and confirm the results.

A review of the traditional and modern uses of Salvadora persica L. (Miswak): Toothbrush tree of Prophet Muhammad.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvadora persica L., also known as Arak (in Arabic) and Peelu (in Urdu), is the most common traditional source of tooth or chewing stick (miswak) highly recommended by Prophet Muhammad. To date, extensive studies have probed primarily into the validation of its traditional uses in oral care. Nonetheless, there is still a dearth of updated compilation and critical analysis of other potential ethnopharmacological properties of S. persica. This review therefore aims to provide an up-to-date detailed structured description of the traditional uses of S. persica and a critical analysis of its modern uses, highlighting its phytochemistry, pharmacological properties, and bioapplications. MATERIALS AND METHODS: Various databases (Science Direct, PubMed, Wiley Online Library, and Google Scholar), books, and relevant primary sources were probed, surveyed, analysed, and included in this review. The literature cited in this review dated from 1979 to 2017. RESULTS: S. persica was found to possess a plethora of bioactive compounds and broad pharmacological properties, including antimicrobial, antioxidant, enzyme inhibitory activity, antiulcer, anticonvulsant, sedative, analgesic, anti-inflammatory, hypoglycemic, hypolipidemic, antiosteoporosis, and antitumor activities. Studies also revealed the potential use of S. persica as a natural food preservative and a novel functional food ingredient. In addition, improvement in growth and reproductive performances have been observed by the introduction of S. persica in animal feed. Lastly, S. persica has also been used in the green synthesis of nanoparticles showing potential biotechnological applications. CONCLUSION: S. persica showed a wide scope of application and its uses have been extended far beyond the initial traditional uses of its roots, stems, and twigs in oral care. We found a number of other ethnopharmacological uses and potential bioapplications of different parts of S. persica that warrants further investigations. Though widely studied using several in vitro and in vivo models, and tested clinically for oral hygiene mainly, several gaps and research priorities have been identified which needs to be addressed in future.

Protective effects of syringin against lipopolysaccharide-induced acute lung injury in mice.

BACKGROUND: Syringin, a major active substance isolated from Eleutherococcus senticosus, has been found to have anti-inflammatory effect. The aim of this study was to investigate the effects and underlying mechanisms of syringin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: We established an LPS-induced ALI model in mice. We also detected the lung wet-to-dry ratio, myeloperoxidase activity, and inflammatory cytokines tumor necrosis factor alpha, interleukin (IL)-1ß, and IL-6 to estimate the index of lung injury in mice. Furthermore, the expression of nuclear factor-erythroid 2-related factor-2 (Nrf2), heme oxygenase-1, and nuclear factor κB (NF-κB) was detected by Western blot analysis. RESULTS: The results showed that the increases in lung wet-to-dry ratio, myeloperoxidase activity, malondialdehyde content, and levels of tumor necrosis factor alpha, IL-1ß, and IL-6 induced by LPS were significantly inhibited by treatment of syringin. The phosphorylation of IκB-α and p65 NF-κB caused by LPS was inhibited by syringin. Furthermore, syringin was found to upregulate the expression of Nrf2 and heme oxygenase 1. CONCLUSIONS: In conclusion, the results suggest that syringin protects against LPS-induced ALI by activating Nrf2 and inhibiting NF-κB signaling pathway.

In vitro culture and production of syringin and rutin in Saussurea involucrata (Kar. et Kir.) - an endangered medicinal plant.

BACKGROUND: Saussurea involucrata (Kar. et Kir.) commonly known as 'snow lotus' or 'Xue Lian' is an important plant in the traditional Chinese system of medicine. The plant contains flavonoids such as syringin and rutin. These compounds have been reported to be anti-rheumatic, anti-inflammatory and dilate blood vessels, lower blood pressure, prevent cardiovascular diseases, enhance immunity, and act as anti-aging, anti-cancer, and anti-fatigue agents. The species has become endangered due to the excessive collection of S. involucrata plants in the wild, slower plant growth and ecological destruction of natural habitats. There is a severe shortage of plant material, while the market demand is ever increasing. Hence, it is very important to apply tissue culture technique for plant propagation and production of the bioactive compounds of this species. RESULTS: Multiple shoot induction and proliferation in shoot base explants derived from in vitro raised seedlings of S. involucrata was achieved on 3/4 strength of Murashige and Skoog's (MS) basal medium (MSBM) supplemented with 1.0 mg/L-1 BA and 1.5 mg/L-1 NAA. Rooting was induced in 100 % shoots cultured on 1/2X MSBM supplemented with 1.0 mg/L-1 IBA for one week and then transfer to auxin free medium. The plantlets could be acclimatized successfully by sachet technique and established in the greenhouse. Maximum callus induction and proliferation in leaf segments was achieved on 1/2X MSBM supplemented with 0.5 mg/L-1 BA, 0.5 mg/L-1 NAA, 0.4 % gelrite and on incubation at 20 °C. Container closures had an influence on the quality and quantity of callus and production of the active compounds. The HPLC analysis showed much higher syringin content in in vitro shoots and callus as compared to commercially available market crude drug. CONCLUSION: The present study describes an in vitro culture protocol of Saussurea involucrata. The bioactive compounds, syringin and rutin could be produced through tissue culture technique without sacrificing the endangered Saussurea involucrata plants in the wild.

Quality Evaluation of Cortex Ilicis Rotundae Medicinal Materials / 广州中医药大学学报

Objective To investigate and evaluate the quality of Cortex Ilicis Rotundae medicinal materials in Chinese herbal medicine market. Methods Twenty-two batches of Cortex Ilicis Rotundae commercial medicinal materials were identified and analyzed by characteristic identification, microscopic identification, thin layer chromatography ( TLC) and extractives determination, and the contents of syringin and pedunculoside were detected by high performance liquid chromatography (HPLC) according to the Chinese Pharmacopoeia published in 2010. And then the quality of the medicinal material of Cortex Ilicis Rotundae was evaluated comprehensively. Results Of the 22 batches of Cortex Ilicis Rotundae medicinal materials, 2 batches were adulterated with fake Cortex Ilicis Rotundae, one batch was inferior and was mixed with counterfeits, and the quality of 12 batches was also poor. Conclusion At present, the quality of Cortex Ilicis Rotundae medicinal materials in Chinese herbal medicine market varies greatly, and adulterants and the inferior are common.

Hepatoprotective effects of syringin on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice.

The prognosis for fulminant hepatic failure (FHF) still remains extremely poor with a high mortality and, therefore, better treatments are urgently needed. Syringin, a main active substance isolated from Eleutherococcus senticosus, has been reported to exhibit immunomodulatory and anti-inflammatory properties. In this study, we investigated the effects and underlying mechanisms of syringin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced FHF in mice. Mice were administered syringin (10, 30 and 100 mg kg(-1), respectively) intraperitoneally (i.p) 30 min before LPS/D-GalN then mortality and liver injury were evaluated subsequently. We found that syringin dose-dependently attenuated LPS/D-GalN-induced FHF, as indicated by reduced mortality, inhibited aminotransferase and malondialdehyde (MDA) content, an increased glutathione (GSH) concentration and alleviated pathological liver injury. In addition, syringin inhibited LPS/D-GalN-induced hepatic caspase-3 activation and hepatocellular apoptosis, myeloperoxidase (MPO) activity and intercellular adhesion molecule-1 (ICAM-1) expression, as well as hepatic tissues tumor necrosis factor-alpha (TNF-α) production and NF-κB activation in a dose-dependent manner. These experimental data indicate that syringin might alleviate the FHF induced by LPS/D-GalN through inhibiting NF-κB activation to reduce TNF-α production.