Resveratrol inhibits oxidative damage in lungs of heat-stressed broilers by activating Nrf2 signaling pathway and autophagy.

The purpose of this study was to investigate the effects of resveratrol on heat stress-induced lung injury in broilers and the mechanism underlying this process. Sixty two-week-old SPF BWEL broilers were randomly divided into the heat stress group (HS), resveratrol group (heat stress + 400 mg/kg resveratrol), and the control group after one week of feeding, with 20 chickens in each group. Broilers in the control group were reared at 23 ± 2 â„ƒ. Those in the HS and resveratrol group were reared under heat stress (35 â„ƒ ± 2 â„ƒ) for 8 h/day for seven days. Broilers in the resveratrol group were fed a diet supplemented with 400 mg/kg resveratrol two days before the start of the experiment. The feeding was continued for nine days. The results showed that HS decreased body weight (BW), average daily feed intake (ADFI), average daily gain (ADG), and lung weight. It, however, increased the lung index, induced lung congestion, and promoted infiltration of inflammatory cells to the lung. Resveratrol improved growth performance and inhibited heat stress-induced lung damage. Compared with broilers in the control group, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), Beclin-1, LC3 Ⅰ, and LC3 Ⅱ genes in the lung of heat-stressed broilers was significantly lower. The levels of kelch-like ECH-associated protein 1 (Keap1), NQO1, and HO-1 showed a similar trend with gene expressions. Immunofluorescence indicated that HS inhibited the expression of Nrf2 and LC3B proteins. Finally, the ratio of LC3 Ⅱ/LC3 Ⅰ was also significantly lower in the HS group. Further analyses revealed that resveratrol supplements in feeds enhanced antioxidation in the lung by activating the Nrf2 signaling pathway and autophagy. In conclusion, HS causes oxidative damage and inhibits autophagy in broilers. However, resveratrol protects against lung injury by alleviating oxidative stress and enhancing autophagy.

Hypericin: A natural anthraquinone as promising therapeutic agent.

BACKGROUND: Hypericin is a prominent secondary metabolite mainly existing in genus Hypericum. It has become a research focus for a quiet long time owing to its extensively pharmacological activities especially the anti-cancer, anti-bacterial, anti-viral and neuroprotective effects. This review concentrated on summarizing and analyzing the existing studies of hypericin in a comprehensive perspective. METHODS: The literature with desired information about hypericin published after 2010 was gained from electronic databases including PubMed, SciFinder, Science Direct, Web of Science, China National Knowledge Infrastructure databases and Wan Fang DATA. RESULTS: According to extensive preclinical and clinical studies conducted on the hypericin, an organized and comprehensive summary of the natural and artificial sources, strategies for improving the bioactivities, pharmacological activities, drug combination of hypericin was presented to explore the future therapeutic potential of this active compound. CONCLUSIONS: Overall, this review offered a theoretical guidance for the follow-up research of hypericin. However, the pharmacological mechanisms, pharmacokinetics and structure activity relationship of hypericin should be further studied in future research.

Resveratrol relieves chronic heat stress-induced liver oxidative damage in broilers by activating the Nrf2-Keap1 signaling pathway.

Heat stress (HS) affects poultry production and welfare, causing enormous damage to poultry. Resveratrol, an antioxidant and anti-inflammatory natural plant polyphenol, is widely used in agriculture for the prevention of oxidative stress-related diseases. This study aimed to explore the effects and potential mechanism of resveratrol on liver oxidative damage in heat-stressed broilers. Sixty SPF chickens were randomly divided into control, heat stress (HS) and HS+ resveratrol (resveratrol) groups. Broilers were exposed to 35 ± 2 â„ƒ (8 h/d) for 7 consecutive days to induce HS, and the other 16 h/d were kept at 23 ± 2 â„ƒ, similar to the control group. Broilers received 400 mg/kg resveratrol in the basic diet 2 days before exposure to HS and for the following 7 days. The results showed that resveratrol improved growth performance by increasing the average daily gain (ADG) and reducing the feed conversion ratio (FCR), compared with the HS group. Heat stress reduced liver weight and index, increased inflammatory cell infiltration in the liver, enhanced serum AST levels, and decreased TP and ALB II levels, which resulted in liver injury in broilers, and resveratrol effectively alleviated liver injury. Moreover, supplementation with resveratrol enhanced the activities of liver antioxidant enzymes resulting in higher GPX and SOD levels than those in the heat-stressed broilers, and decreased MDA levels. Furthermore, resveratrol alleviated liver oxidative stress by activating the gene and protein levels of Nrf2 and HO-1, enhancing NQO1 and SOD1 gene levels, and decreasing protein levels of HSP70, p62, and Keap1, and thereby alleviated the liver injury of heat-stressed broilers. Compared with the HS group, Nrf2 immunofluorescence was significantly up-regulated in the livers of resveratrol group. These results suggest that resveratrol can enhance the liver antioxidant function by activating the Nrf2-Keap1 signaling pathway to promote growth performance in broilers under HS.

Hyperforin: A natural lead compound with multiple pharmacological activities.

Hypericum perforatum L. (Clusiaceae), commonly known as St. John's wort, has a rich historical background as one of the oldest and most widely studied herbal medicines. Hyperforin is the main antidepressant active ingredient of St. John's wort. In recent years, hyperforin has attached increasing attention due to its multiple pharmacological activities. In this review, the information on hyperforin was systematically summarized. Hyperforin is considered to be a lead compound with diverse pharmacological activities including anti-depression, anti-tumor, anti-dementia, anti-diabetes and others. It can be obtained by extraction and synthesis. Further pharmacological studies and more precise detection methods will help develop a value for hyperforin. In addition, structural modification and pharmaceutical preparation technology will be beneficial to promoting the research progress of hyperforin based innovative drugs. Although these works are full of known and unknown challenges, researchers are still expected to make hyperforin play a greater value.

Xianglian Pill attenuates ulcerative colitis through TLR4/MyD88/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear. AIM OF THE STUDY: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice. MATERIALS AND METHODS: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1ß, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4-/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms. RESULTS: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1ß, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4-/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis. CONCLUSIONS: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway.

[Effects of electroacupuncture at "Zhongliao" and "Xialiao" on serotonin signaling system and short-chain fatty acids in slow transit constipation rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zhongliao" (BL33) and "Xialiao" (BL34) on the 5-hydroxytryptamine (5-HT) signaling system in colon tissue and short-chain fatty acids in feces of rats with slow transit constipation (STC), so as to explore the underlying mechanisms of EA in the treatment of STC. METHODS: A total of 32 SD rats were randomly divided into normal, model, drug control and EA groups, with 8 rats in each group. The STC model was established by intragastric administration of loperamide for 14 days. The EA stimulation (2 Hz/15 Hz) was performed at bilateral BL33 and BL34 for 30 min, once a day for 14 days. The first black stool de-fecation time and fecal water content were detected after treatment. The expressions of 5-hydroxytryptamine 4 receptor (5-HT4R), tryptophan hydroxylase 1 (TPH1) and 5-HT transporter (SERT) in colon tissues were detected by Western blot. The contents of substance P (SP) and vasoactive intestinal peptide (VIP) in serum were detected by ELISA. The contents of 5-HT in colon tissue and short chain fatty acid (SCFA) in feces were detected by mass spectrometry. RESULTS: Compared with the normal group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissue, the content of serum SP were significantly decreased (P<0.05), the first black stool de-fecation time, and the content of serum VIP was significantly increased (P<0.05), the contents of SCFA in feces were significantly decreased except isobutyric acid (P<0.05) in the model group. Compared with the model group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissues, the contents of acetic acid and butyrate in feces were significantly increased (P<0.05) in the EA and drug control groups, the first black stool defecation time was decreased (P<0.05) in the EA and drug control groups, and the content of serum SP was increased and the content of serum VIP was decreased (P<0.05) in the EA group. Compared with the drug control group, the content of serum VIP was significantly decreased (P<0.05), and the expressions of TPH1 and SERT in colon tissue were significantly increased (P<0.05) in the EA group. CONCLUSION: EA at BL33 and BL34 can promote intestinal motility by intervening multiple links of 5-HT signaling system in treating STC.

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice.

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

ACSL4 promotes colorectal cancer and is a potential therapeutic target of emodin.

BACKGROUND: Colorectal cancer (CRC) is an important death-related disease in the world and new therapeutic strategies are urgently needed to reduce mortality. Several studies have demonstrated that emodin, the main ingredient of Rheum palmatum, fights cancer but its potential anti-tumor effect on CRC is still unknown. PURPOSE: The present study is aimed to explore the potential anti-tumor effects of emodin against CRC and the underlying molecular mechanism. METHODS: CRC-related datasets were screened according to filter criteria in the GEO database and TCGA database. By using screened differentially expressed genes, GO, KEGG and survival analysis were carried out. The expressions of ACSL4, VEGFR1, and VEGFR2 were examined by immunohistochemistry and western blot. Then, pcDNA-ACSL4, pcDNA-VEGFR1, and pcDNA-VEGFR2 were used to overexpress ACSL4, VEGFR1, and VEGFR2, while ACSL4 siRNA was used to silence ACSL4 expression in HCT116 cells. CCK-8 assay and transwell migration assay were used to detect the cell proliferation and invasion. A docking simulation assay and an MST assay were performed to explore the potential mode of emodin binding to ACSL4. The HCT116 cells and CRC mouse model were established to investigate the effects of emodin on CRC. RESULTS: The ACSL4, VEGFR1, and VEGFR2 expression were upregulated in CRC tissues and ACSL4 was associated with a shorter survival time in CRC patients. ACSL4 downregulation reduced cell proliferation and invasion, while ACSL4 exhibited a positive correlation with the levels of VEGFR1, VEGFR2, and VEGF. In HCT116 cells, emodin reduced cell proliferation and invasion by inhibiting ACSL4, VEGFR1, and VEGFR2 expression and VEGF secretion. Docking simulation and MST assay confirmed that emodin can directly bind to ACSL4 target. Moreover, ACSL4 overexpression abolished the inhibitory effect of emodin on VEGF secretion and VEGFR1 and VEGFR2 expression, but VEGFR1 and VEGFR2 overexpression did not affect the inhibitory effect of emodin on ACSL4 expression and VEGF secretion. Furthermore, emodin reduced the mortality and tumorigenesis of CRC mice and reduced ACSL4, VEGFR1, VEGFR2 expression, and VEGF content. CONCLUSION: Our findings indicate that emodin inhibits proliferation and invasion of CRC cells and reduces VEGF secretion and VEGFR1 and VEGFR2 expression by inhibiting ACSL4. This emodin-induced pathway offers insights into the molecular mechanism of its antitumor effect and provides a potential therapeutic strategy for CRC.

The bibenzyl derivatives of Dendrobium officinale prevent UV-B irradiation induced photoaging via SIRT3.

Dendrobium officinale is a valuable medicinal herb that is widely used in traditional Chinese medicine. The chemical constituents of D. officinale have attracted much attention and a large number of compounds have been reported including many bibenzyl derivatives. 13 bibenzyl derivatives from D. officinale were sent for molecular docking, surface plasmon resonance (SPR) assay and after detection of Mn-SOD and SIRT3 activities in or not in HaCaT cells, it was concluded that bibenzyl derivatives did not directly activate Mn-SOD but promoted SIRT3 proteins. In addition, HaCaT cells were irradiated with UV-B to induce an oxidative stress model in vitro to further verify the effect of bibenzyl derivatives. The results show that bibenzyl derivatives could directly bind to SIRT3, enhance the deacetylation and then activate Mn-SOD, so as to protect UV-B induced skin photoaging.

Ding's herbal enema treats dextran sulfate sodium-induced colitis in mice by regulating the gut microbiota and maintaining the Treg/Th17 cell balance.

Ding's herbal enema (DHEP) is a traditional Chinese medicinal therapy that has been used to treat ulcerative colitis (UC) in China. The present study determined the molecular mechanism of the effect of DHEP in UC treatment. C57BL/6J mice were treated with 3.5% (w/v) dextran sulfate sodium (DSS) for 7 days to establish an animal model of colitis. The mice were divided into five groups (n=5): Control, vehicle, DHEP, mesalazine and ß-sitosterol. After oral administration for 7 days, the body weight, disease activity index, histopathology and inflammatory factors were analyzed. The fractions of CD4+Foxp3+ regulatory T (Treg) cells and CD4+IL-17A+ T helper (Th) cells were determined by flow cytometry. Gut microbiota composition was analyzed by next-generation sequencing. The results revealed that DHEP and ß-sitosterol could significantly alleviate the symptoms of DSS-induced UC. Furthermore, the levels of IL-6, cyclooxygenase-2, TNF-α and p65 were reduced after administration of DHEP. Additionally, the data indicated that DHEP could increase the abundance of seven operational taxonomic units (OTUs) and decrease the abundance of 12 OTUs in the gut microbiota. The content of short-chain fatty acids in the colon remodeled the balance of Treg/Th17 cells in DSS-induced UC in mice. The present study preliminarily defined the mechanism of action of DHEP in UC that may be associated with the regulation of the gut microbiota composition, and maintenance of the balance between Treg and Th17 cells. Furthermore, ß-sitosterol exhibited the same effects with DHEP and it could be a possible substitute for DHEP in UC treatment.

Effect of local ozone treatment on rats with anterior rectal resection and the possible mechanisms.

BACKGROUND: Anterior resection syndrome (ARS) is characterized by the diverse and interchangeable evacuatory symptoms that may occur following distal colorectal resection. We aimed to investigate the effect and potential mechanisms of ozone perfusion on rats with anterior rectal resection (ARR). MATERIAL AND METHODS: After establishment of rat ARR model, 20, 40 and 80 ug/ml ozone was used to treat rats by enema administration. The pathological examination of intestinal tissue was detected using hematoxylin-eosin staining. The rate of loose stools, minimum threshold volume of abdominal withdrawal reflex (AWR) and Bristol grade were used to evaluate the degree of abnormal defecation function. Subsequently, the levels of oxidative stress- and inflammation-related markers, 5-hydroxytryptamine (5-HT), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the serum and intestinal tissue were determined with the corresponding kits. Meanwhile, the expression of nuclear factor kappa B (NF-κB) p65, transient receptor potential vanilloid (TRPV)1, TRPV4, iNOS and 5-HT receptor 3A (5-HTR3A) was determined with RT-qPCR and western blotting. RESULTS: Ozone administration (20 and 40 ug/ml) significantly alleviated the pathological changes of intestinal tissue-induced by ARR, accompanied by the decreased loose stools rate, Bristol score and increased abdominal withdraw reflex. However, 80 ug/ml of ozone intervention played opposite roles in the aforementioned changes with 20 and 40 ug/ml of ozone. Additionally, remarkably elevated reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), 5-HT, iNOS and NO levels were observed in the ozone-treated groups (20 and 40 ug/ml), while high dose of ozone drastically improved ROS, MDA, 5-HT, iNOS and NO levels but reduced the activity of SOD. Consistently, the contents of inflammatory factors were decreased after low and middle doses of ozone administration. However, high dose of ozone aggravated the inflammatory injury. Moreover, 20 and 40 ug/ml ozone upregulated TRPV1 and TRPV4 expression but downregulated 5-HTR3A expression, which was restored after 80 ug/ml of ozone intervention. Remarkably, the levels of NF-κB p65 and iNOS were dose-dependently enhanced following ozone treatment. CONCLUSIONS: Taken together, low concentration of ozone attenuated intestinal injury induced by ARR via balancing oxidative stress and inflammation, but high concentration of ozone exacerbated the intestinal injury, which might be related to the 5-HT and TRPV signaling.

Chai Hu oral liquid enhances the immune functions of both spleen and bursa of Fabricius in heat-stressed broilers through strengthening TLR4-TBK1 signaling pathway.

Heat stress can affect the poultry production and immune status of broilers. Heat stress disrupts intestinal integrity and increases intestinal inflammation, which is related with body immune dysfunction. Chai Hu oral liquid used as an antipyretic and anti-inflammatory drug is widely used in exogenous fever of poultry, but its resistance to heat stress and the mechanism is still unclear. In this study, a chronic heat stressed broilers model was established to explore the mechanisms of broilers' immune function changes and the effects of Chai Hu oral liquid. In this study, a total of 480 broilers were randomly divided into 6 groups with 80 replicates. Heat stress (HS) group broilers were stressed at 35 ± 2°C for 5 or 10 consecutive d with 6 h/d. Heat stressed (for 5 or 10 d) broilers were given with Jieshu KangreSan (Positive), Chai Hu oral liquid high, middle and low dosage (CH-High, CH-Mid, CH-Low) by oral administration. Birds in control group were treated with the same volume of PBS only in 25 ± 2°C. All birds were sacrificed at last heat stress challenged day. Changes in immune function were assessed by immune organs index, serum IFN-γ level, gene and protein expressions of immune factors in spleen and bursa of Fabricius. Results from this experiment showed that heat stress enhanced the immune organs' edema by directly increased the organs indexes of spleen and bursa of Fabricius in broilers. Heat stress for 10 d also increased bursa of Fabricius HSP70 protein level and significantly lowered the spleen and bursa of Fabricius proteins expressions of IFN-α, IFN-ß, and IFN-γ in broilers. The IFN-ß and IFN-γ protein levels in spleen and bursa of Fabricius also decreased in heat stressed broilers for 5 d. The gene and protein expressions of TLR4 and TBK1 markedly decreased in spleen and bursa of Fabricius of broilers treated with chronic heat stress. Chai Hu oral liquid reduced edema of immune organs and elevated TLR4-TBK1 signaling pathway to release immune factors. Above results indicated that chronic heat stress induced impaired immune function by inhibiting TLR4-TBK1 signaling pathway, and Chai Hu oral liquid had effective protection of body's immune ability by enhancing this signaling pathway.

Existing knowledge on Euphorbia fischeriana Steud. (Euphorbiaceae): Traditional uses, clinical applications, phytochemistry, pharmacology and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia fischeriana Steud. (Euphorbiaceae) is a perennial herb distributed in grassland, hill slopes or gravel hillside, with average altitude of 100-600 m. The whole grass of E. fischeriana is toxic with roots used as folk medicine to treat Zhushui, dyspepsia, abdominal distension, abdominal pain, cough, as well as external applications such as cure of scabies and tuberculosis of lymph nodes. AIM OF THE REVIEW: This systematic review aims to provide a detailed and in-depth summary about the reported advances in traditional uses, clinical applications, phytochemistry, pharmacology and toxicity of E. fischeriana, so as to offer fresh ideas and broader vision and insights for subsequent studies. MATERIALS AND METHODS: Various scientific data bases such as CNKI, Elsevier, Google Scholar, Pubmed, Science Direct, SciFinder Scholar and Web of Science were searched to collect information about E. fischeriana. Other relevant literatures were searched in 'Flora of China Editorial Committee', ancient books, Ph.D and Masters' Dissertation to get more data of E. fischeriana. RESULTS: A total of 241 chemical constituents have been identified from the roots of E. fischeriana, including diterpenoids, triterpenoids, meroterpenoids, acetophenones, flavonoids, coumarins, steroids, phenolic acids, tannins, etc. Various pharmacological activities have been demonstrated, especially anti-tumor, antibacterial, anti-inflammatory, antiviral and anti-leukemia activities. Moreover, different investigations about clinical uses and toxicology of E. fischeriana indicated that attention should be paid to its usage and dosage. CONCLUSION: The researches of E. fischeriana are excellent, but gap still remains. As a poisonous traditional Chinese medicine, there are not enough studies on the toxicity of E. fischeriana. In addition, scholars' research on the pharmacological mechanism of E. fischeriana focuses more on the anti-tumor activity, which can be broadened in the future. Presumably, chemical constituents and biological activities of diterpenoids and trace meroterpenoids in E. fischeriana deserve further research in-depth in the future, in order to provide low toxicity and high efficiency lead compounds. Meanwhile, further studies on other medicinal aspects may lay a foundation for the comprehensive development and utilization of E. fischeriana.

Ethnopharmacology, phytochemistry, pharmacology, clinical applications and toxicology of the genus Stellera Linn.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Stellera Linn. consists of species of perennial herbs and shrubs, and is mainly distributed in the temperate regions of east Asia to west Asia. There are 10∼12 species in the world, two species in China: Stellera chamaejasme Linn. and Stellera formosana Hayata ex Li. As recorded, the roots of Stellera species are used to dissipate phlegm and relieve pain. The roots and the barks can be used for papermaking. AIM OF THIS REVIEW: This review aims to summarize the ethnopharmacological uses, chemical constituents, pharmacological activities, clinical applications and toxicology of the genus Stellera to better understand their therapeutic potential in the future. MATERIALS AND METHODS: The relevant information of the genus Stellera was collected from scientific databases (Pubmed, ACS website, SciFinder Scholar, Elsevier, Google Scholar, Web of Science and CNKI). Information was also gathered from 'Flora Republicae Popularis Sinicae (〈〈〉〉)', folk records, conference papers on ethnopharmacology, Ph.D. and Masters' Dissertation. RESULTS: Stellera plants have been studied as traditional folk medicines all around the world. The chemical constituents of Stellera species mainly comprise terpenoids, flavonoids, coumarins, lignans, and so on. Extracts and compounds of Stellera species exhibit extensive pharmacological activities, such as anti-tumor, anti-viral, anti-convulsive, anti-epileptic, anti-bacterial and anti-insect activities, etc. Clinical applications have suggested that the genus Stellera has the effects in treating several skin diseases and cancers, however, the results should be further verification. The genus Stellera plants are toxic and should be used reasonable. CONCLUSION: This paper reviewed the ethnopharmacological uses, chemical constituents, pharmacology, clinical applications and toxicology of the genus Stellera. The genus Stellera has broad application prospects. However, further in-depth studies are needed to determine the medical uses of the genus and its chemical constituents, pharmacological activities, clinical applications and toxicology.

Qian Yang Yu Yin Granule-containing serum inhibits angiotensin II-induced proliferation, reactive oxygen species production, and inflammation in human mesangial cells via an NADPH oxidase 4-dependent pathway.

BACKGROUND: Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese herbal medicine, has been indicated for renal damage in hypertension for decades in China, but little remains known regarding its underlying molecular mechanism. Therefore, we performed the current study in order to investigate the underlying molecular mechanism of QYYYG in the treatment of hypertensive renal damage. METHODS: We hypothesize that QYYYG relieves hypertensive renal injury through an angiotensin II (Ang II)-nicotinamide adenine dinucleotide phosphate (NAPDH)-oxidase (NOX)-reactive oxygen species (ROS) pathway. In this study, we investigated the effects of QYYYG-containing serum (QYGS) in human mesangial cells (HMCs) against Ang II-induced cell proliferation, ROS production, and inflammation through the seropharmacological method. RESULTS: We found that QYGS could inhibit cell proliferation in Ang II-treated HMCs. In addition, QYGS considerably suppressed production of ROS, decreased mRNA and protein expression of NAPDH-oxidase 4 (NOX4), p22 (phox) , and activated Ras-related C3 botulinum toxin substrate 1 (GTP-Rac1); as well as counteracted the up-regulation of inflammatory markers including tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) p65, and interleukin 6 (IL-6). These effects were further confirmed in HMCs transfected with specific small interfering RNA (siRNA) targeting NOX4. CONCLUSIONS: Taken together, these results suggest that a NOX4-dependent pathway plays an important role in regulating the inhibitory effect of QYGS. Our findings provide new insights into the molecular mechanisms of QYYYG and their role in the treatment of hypertensive nephropathy.

[Clinical observation on the safety and efficacy of ursodeoxycholic acid and fuzheng huayu capsule in the treatment of primary biliary cirrhosis].

OBJECTIVE: To observe the clinical efficacy of ursodeoxycholic acid (UDCA) and Fuzheng Huayu Capsule (FHC) in the treatment of primary biliary cirrhosis (PBC). METHODS: Eighty PBC patients were randomly assigned to two groups, the treatment group and the control group, 40 in each group. Patients in the treatment group took UDCA and FHC, while those in the control group were treated with UDCA alone. The treatment course was 48 weeks for both groups. The clinical symptoms and signs, liver function indices (ALT, AST, ALP, GGT, ALB, TBIL, and TBA), hepatic fibrosis indices (HA, LN, IV-CL, and PIIIP), immunologic indices (IgG, IgM, and autoimmune antibodies), changes of portal hemodynamics, and adverse reactions were observed before treatment, as well as at week 4, 12, 24, and 48 after treatment. RESULTS: After treatment the skin itching and fatigue were significantly improved in the treatment group, showing statistical difference when compared with the control group (P < 0.05, P < 0.01). After treatment the levels of ALT, AST, ALP, GGT, TBIL, and TBA obviously decreased in the two groups. They were lower in the treatment group than in the control group at the same time point (P < 0.05). The decrement was the largest at week 4. Besides, at week 48 after treatment the ALB level was improved in the treatment group (P < 0.05). The levels of HA and PIIIP obviously decreased at week 4, 12, and 24, the levels of LN and IV-C obviously decreased at week 4 and 12, the decrement of the hepatic fibrosis indices at week 4 were more obvious in the treatment group. But the levels of HA and PIIIP were lower than the pre-treatment levels at week 12 in the control group. The immunologic indices such as IgM and IgG were improved in the two groups, with better results obtained in the treatment group (P < 0.05, P < 0.01). In the treatment group ANA turned negative in 1 patient and AMA turned negative in 2 patients. After 48 weeks of treatment, the spleen was retracted, the inner diameters of the portal vein (PV) and the splenic vein (SV) were significantly reduced, and the blood flow velocity in the PV and SV increased in the treatment group (P < 0.01). At week 24 and 48, 33 patients (82.5%) and 26 patients (90.0%) in the treatment group had complete relief, better than those of the control group [22 cases (55.0%) and 28 cases (70.0%)]. No obvious adverse reaction was found in the two groups during the treatment course. CONCLUSIONS: The combination therapy of UDCA and FHC was effective and safe in anti fibrosis and improving the liver functions of PBC patients. It was safe and better than the application of UDCA alone. It was advocated to be combined use for a long term. It might improve the long-term efficacy.

Clinical observation on the safety and efficacy of ursodeoxycholic acid and fuzheng huayu capsule in the treatment of primary biliary cirrhosis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of ursodeoxycholic acid (UDCA) and Fuzheng Huayu Capsule (FHC) in the treatment of primary biliary cirrhosis (PBC).</p><p><b>METHODS</b>Eighty PBC patients were randomly assigned to two groups, the treatment group and the control group, 40 in each group. Patients in the treatment group took UDCA and FHC, while those in the control group were treated with UDCA alone. The treatment course was 48 weeks for both groups. The clinical symptoms and signs, liver function indices (ALT, AST, ALP, GGT, ALB, TBIL, and TBA), hepatic fibrosis indices (HA, LN, IV-CL, and PIIIP), immunologic indices (IgG, IgM, and autoimmune antibodies), changes of portal hemodynamics, and adverse reactions were observed before treatment, as well as at week 4, 12, 24, and 48 after treatment.</p><p><b>RESULTS</b>After treatment the skin itching and fatigue were significantly improved in the treatment group, showing statistical difference when compared with the control group (P < 0.05, P < 0.01). After treatment the levels of ALT, AST, ALP, GGT, TBIL, and TBA obviously decreased in the two groups. They were lower in the treatment group than in the control group at the same time point (P < 0.05). The decrement was the largest at week 4. Besides, at week 48 after treatment the ALB level was improved in the treatment group (P < 0.05). The levels of HA and PIIIP obviously decreased at week 4, 12, and 24, the levels of LN and IV-C obviously decreased at week 4 and 12, the decrement of the hepatic fibrosis indices at week 4 were more obvious in the treatment group. But the levels of HA and PIIIP were lower than the pre-treatment levels at week 12 in the control group. The immunologic indices such as IgM and IgG were improved in the two groups, with better results obtained in the treatment group (P < 0.05, P < 0.01). In the treatment group ANA turned negative in 1 patient and AMA turned negative in 2 patients. After 48 weeks of treatment, the spleen was retracted, the inner diameters of the portal vein (PV) and the splenic vein (SV) were significantly reduced, and the blood flow velocity in the PV and SV increased in the treatment group (P < 0.01). At week 24 and 48, 33 patients (82.5%) and 26 patients (90.0%) in the treatment group had complete relief, better than those of the control group [22 cases (55.0%) and 28 cases (70.0%)]. No obvious adverse reaction was found in the two groups during the treatment course.</p><p><b>CONCLUSIONS</b>The combination therapy of UDCA and FHC was effective and safe in anti fibrosis and improving the liver functions of PBC patients. It was safe and better than the application of UDCA alone. It was advocated to be combined use for a long term. It might improve the long-term efficacy.</p>