The nanomaterials with enzyme-like catalytic activity, named as nanozymes, have aroused wide research interest owing to their striking merits. Metal-organic frameworks (MOFs) have showed great prospect in the construction of novel nanozymes. In this review, firstly, we summarize the most recent contributions in the design construction of the MOFs-based nanozymes. Then, we concentrate our attention on their applications in the fields of sensing and cancer therapies. According to the design strategies, we categorized MOFs-based nanozymes into four classes for review (i.e. pristine MOFs, MOFs with modification, MOFs-based nanocomposites, and MOF derivatives). Meanwhile, the emerging and fascinating 2D MOFs-based nanozymes were also reviewed. A variety of novel applications are also discussed, including nanozymes catalytic mediated signal amplification in sensing applications (e.g. colorimetric sensing, fluorescent sensing, chemiluminescent sensing, electrochemical sensing, and surface-enhanced Raman scattering (SERS)), and nanozymes catalytic mediated cancer therapy (i.e. cancer-starvation therapy, enhancing photodynamic therapy, and cancer-starvation and PDT synergistic therapy). At the end of the article, future opportunities and challenges in this promising research area are tentatively proposed.
Tibetan medicine "Dida" isoccasionally misused due to its complex origins, which ultimately affects its clinical efficacy. The accurate name, origin, property, and efficacy of "Dida"are highly important for its further research and development. In the present study, by viewing the classic Tibetan medicine and modern literature, and combining the clinical practice of Tibetan medicine, the origins, properties and the clinic effects of "Dida" were defined. "Dida" originated from multiple plant species of Swertia, Gentianopsis, Halenia, Lomatogonium, Comastoma(Gentianaceae), Hedyotis (Saxifragaceae) and Erysimum (Cruciferae). The medicinal properties of "Dida" is mainly bitter and cold. It has been commonly used to treat febrile diseases and hepatic and gall diseases. This study suggested that the relevant herbalogical study, species identification and pharmacological effects of "Dida" should be taken based on the Tibetan medicine theories and clinical practice. Thus the medicine can be better used and ensure its safety and quality simultaneously.
With the development of Tibetan medicine industry, the demands for Tibetan medicine were rising sharply. In addition, with the eco-environment vulnerability of Qinghai-Tibet Plateau region and the phenomenon of synonymies and homonymies in Tibetan medicine, there were a lack of resources and varieties in the clinical application of Tibetan medicine. At present, the shortage of Tibetan medicine and the inadequacy of its quality standard have become the two major problems that seriously restricted the sustainable development of Tibetan medicine industry. Therefore, it is important to develop the resources investigation and quality evaluation for Tibetan medicine, which were contribute to its resources protection and sustainable utilization. In this paper, current status of resources investigation, quality standardization, artificial breeding and germplasm resources of Tibetan medicine were presented by the integrated application of the new technologies, such as DNA barcoding and 1H-NMR, which provided a reference information for resources protection, sustainable utilization, variety identification and quality standardization of Tibetan medicine resources in Qinghai-Tibet Plateau.
Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness-based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness-based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6-week mindfulness-based resilience training (MBRT) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty-one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health-related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant (P<.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality-of-life mental component (P=.006) and positive affect (P=.02) also improved at follow-up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well-being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.
Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness-based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness-based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6-week mindfulness-based resilience training (MBRT) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty-one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health-related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant (P<.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality-of-life mental component (P=.006) and positive affect (P=.02) also improved at follow-up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well-being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.
Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness-based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness-based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6-week mindfulness-based resilience training (MBRT) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty-one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health-related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant (P<.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality-of-life mental component (P=.006) and positive affect (P=.02) also improved at follow-up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well-being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.
The investigation aims to better understand the resource status of Rhodiola kirilowii, analysis the suitable habitat of wild Rh. kirilowii and protect the wild resources of Rh. Kirilowii, promoting the sustainable utilization of Rh. kirilowii resources. In this paper, we investigated the wild resources of Rh. kirilowii in 16 counties of Sichuan, Qinghai, Gansu and Yunnan by means of investigation and sampling investigation combined with interview. The results showed that the population densities of wild Rh. kirilowii in 4 provinces were very different and the reserve of wild resources decreased gradually in many areas. According to the survey results, the current total reserve of Rh. kirilowii in four provinces was about 1 100 t. The reserve of wild Rh. kirilowii in Sichuan province was the largest. Simultaneously, the Rh. kirilowii had a certain ecological value. We found that a sand control base with planting Rh. kirilowii was set up in Hongyuan County of Sichuan Aba Tibetan and Qiang Autonomous Prefecture. The investigation provides a scientific basis for the development and sustainable utilization of Rh. kirilowii resources.
The resource of Sinopodophyllum emodi in Tibet, Qinghai, Gansu, Sichuan and Yunnan province were surveyed by the ways of documents, interview, quadrat and market investigation. The results indicated that S. emodi were mainly distributed in central part from Taibai Shan of Shanxi province along the middle and high mountain on either side of Hengduan mountain which from north to south and in Tibetan plateau of China, the suitable eco-environment of S. emodi was dominated by valleys, wet forests and low bush-woods vegetation which comparatively dry on plateau with the altitude focused on 1 5004 500 meters, and the distribution density of simple alpine meadow was relatively lower. Illumination, water, soil, temperature and altitude had significant influences on the growth, distribution and reserves of S. emodi from different angles. In recent years, there was sharp increase of market requirement in Xiaoyelian (fruit) which were used in Tibetan medicine and the underground part which was used for the extraction of podophyllotoxin, excess collection of the underground part was the primary cause of the rapid decreasing resource of S. emodi. It is suggested that the management of rational collection should be strengthen and the development of culturing and production should be meanwhile accelerated.
The regulation of postprandial blood glucose (PBG) levels is an effective therapeutic method to treat diabetes and prevent diabetes-related complications. Resveratroloside is a monoglucosylated form of stilbene that is present in red wine, grapes, and several traditional medicinal plants. In our study, the effect of resveratroloside on reducing PBG was studied in vitro and in vivo. In comparison to the starch treatment alone, the oral administration of resveratroloside-starch complexes significantly inhibited the PBG increase in a dose-dependent pattern in normal and diabetic mice. The PBG level treated with resveratrol (30 mg/kg) was not lower than that of resveratroloside. Further analyses demonstrated that resveratroloside strongly and effectively inhibited α-glucosidase, with an 50% inhibitory concentration value of 22.9 ± 0.17 μM, and its inhibition was significantly stronger than those of acarbose and resveratrol (264 ± 3.27 and 108 ± 2.13 μM). Moreover, a competitive inhibition mechanism of resveratroloside on α-glucosidase was determined by enzyme kinetic assays and molecular docking experiments. The molecular docking of resveratroloside with α-glucosidase demostrated the competitive inhibitory effect of resveratroloside, which occupies the catalytic site and forms strong hydrogen bonds with the residues of α-glucosidase. Resveratrol was also determined to be a competitive inhibition mechanism on α-glucosidase by enzyme kinetic assays and molecular docking experiments. This study suggested that resveratroloside had the ability to regulate PBG levels and can be considered a potential agent for the treatment of diabetes mellitus.
ETHNOPHARMOCOLOGICAL RELEVANCE: Herbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries.AIM OF THE REVIEW: This review uses cinnabar (HgS) and realgar (As4S4) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives.
MATERIALS AND METHODS: A literature search on cinnabar and realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out. Traditional medicines containing both cinnabar and realgar (An-Gong-Niu-Huang Wan, Hua-Feng-Dan); mainly cinnabar (Zhu-Sha-An-Shen Wan; Zuotai and Dangzuo), and mainly realgar (Huang-Dai Pian; Liu-Shen Wan; Niu-Huang-Jie-Du) are discussed.
RESULTS: Both cinnabar and realgar used in traditional medicines are subjected to special preparation procedures to remove impurities. Metals in these traditional medicines are in the sulfide forms which are different from environmental mercurials (HgCl2, MeHg) or arsenicals (NaAsO2, NaH2AsO4). Cinnabar and/or realgar are seldom used alone, but rather as mixtures with herbs and/or animal products in traditional medicines. Advanced technologies are now used to characterize these preparations. The bioaccessibility, absorption, distribution, metabolism and elimination of these herbo-metallic preparations are different from environmental metals. The rationale of including metals in traditional remedies and their interactions with drugs need to be justified. At higher therapeutic doses, balance of the benefits and risks is critical. Surveillance of patients using these herbo-metallic preparations is desired.
CONCLUSION: Chemical forms of mercury and arsenic are a major determinant of their disposition, efficacy and toxicity, and the use of total Hg and As alone for risk assessment of metals in traditional medicines is insufficient.
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata, a traditional Tibetan medicine, has shown promise in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, the underlying mechanisms remain unclear. This study investigated the protective effects of R. crenulata aqueous extract (RCAE) on HH-induced brain injury in rats.MATERIALS AND METHODS: An animal model of high-altitude hypoxic brain injury was established in SD rats using an animal decompression chamber for 24 h. Serum and hippocampus levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were then determined using commercial biochemical kits. Neuron morphology and vitality were also evaluated using H&E and Nissl staining, and TUNEL staining was used to examine apoptosis. Gene and protein expression of HIF-1α, microRNA 210, ISCU1/2, COX10, Apaf-1, cleaved Caspase-3, Caspase-3, Bax, Bcl-2, and Cyto-c were determined by western blot, immunohistochemical and qRT-PCR analysis.
RESULTS: RCAE administration attenuated HH-induced brain injury as evidenced by decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, improvements in hippocampus histopathological changes, increased cell vitality and ATP level, and reduced apoptotic cell numbers. RCAE treatment also enhanced HIF-1α, ISCU1/2, COX10, and Bcl-2 protein expression, while dramatically inhibiting expression of Apaf-1, Bax, Cyto-c, and cleaved Caspase-3. Treatment also increased gene levels of HIF-1α, microRNA 210, ISCU1/2, and COX10, and decreased Caspase-3 gene production.
CONCLUSIONS: RCAE attenuated HH-induced brain injury by regulating apoptosis and mitochondrial energy metabolism via the HIF-1α/microRNA 210/ISCU1/2 (COX10) signaling pathway.
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata, a traditional Tibetan medicine, has shown promise in the treatment of hypobaric hypoxia (HH)-induced brain injury. However, the underlying mechanisms remain unclear. This study investigated the protective effects of R. crenulata aqueous extract (RCAE) on HH-induced brain injury in rats. MATERIALS AND METHODS: An animal model of high-altitude hypoxic brain injury was established in SD rats using an animal decompression chamber for 24 h. Serum and hippocampus levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and lactate dehydrogenase (LDH) were then determined using commercial biochemical kits. Neuron morphology and vitality were also evaluated using H&E and Nissl staining, and TUNEL staining was used to examine apoptosis. Gene and protein expression of HIF-1α, microRNA 210, ISCU1/2, COX10, Apaf-1, cleaved Caspase-3, Caspase-3, Bax, Bcl-2, and Cyto-c were determined by western blot, immunohistochemical and qRT-PCR analysis. RESULTS: RCAE administration attenuated HH-induced brain injury as evidenced by decreased levels of MDA, LDH, and GSSG, increased GSH and SOD, improvements in hippocampus histopathological changes, increased cell vitality and ATP level, and reduced apoptotic cell numbers. RCAE treatment also enhanced HIF-1α, ISCU1/2, COX10, and Bcl-2 protein expression, while dramatically inhibiting expression of Apaf-1, Bax, Cyto-c, and cleaved Caspase-3. Treatment also increased gene levels of HIF-1α, microRNA 210, ISCU1/2, and COX10, and decreased Caspase-3 gene production. CONCLUSIONS: RCAE attenuated HH-induced brain injury by regulating apoptosis and mitochondrial energy metabolism via the HIF-1α/microRNA 210/ISCU1/2 (COX10) signaling pathway.
Sub-acute and chronic toxic effects of total steroidal saponins (TSSN) extracts from Dioscorea zingiberensis C.H. Wright on various internal organs and biochemical indicators have never been studied before and this study is the first of its kind to demonstrate sub-acute and chronic toxicities of TSSN on dogs. Administration of TSSN extracts at doses up to 3000 mg/Kg daily for 14 days, no biochemical and organ changes were observed on the experimental groups of dogs. Further, chronic toxicity study through oral administration of TSSN extracts at the gradual doses of 50, 250 and 500 mg/Kg for 90 days followed by a 2-week recovery assay revealed absence of significant architectural and morphological changes in internal organs which were confirmed through histopathological examination and merely no significant alteration in the biochemical indicators including hematologic and urine analysis and electrocardiogram compared to the control dogs. This toxicological evaluation came across with the finding that the herbal preparation can be considered as nontoxic and animals could tolerate the extracts at doses up to 500 mg/Kg with LD50 greater than 3000 mg/Kg. It may serve as a preliminary scientific evidence for further therapeutic investigations.
Sub-acute and chronic toxic effects of total steroidal saponins (TSSN) extracts from Dioscorea zingiberensis C.H. Wright on various internal organs and biochemical indicators have never been studied before and this study is the first of its kind to demonstrate sub-acute and chronic toxicities of TSSN on dogs. Administration of TSSN extracts at doses up to 3000 mg/Kg daily for 14 days, no biochemical and organ changes were observed on the experimental groups of dogs. Further, chronic toxicity study through oral administration of TSSN extracts at the gradual doses of 50, 250 and 500 mg/Kg for 90 days followed by a 2-week recovery assay revealed absence of significant architectural and morphological changes in internal organs which were confirmed through histopathological examination and merely no significant alteration in the biochemical indicators including hematologic and urine analysis and electrocardiogram compared to the control dogs. This toxicological evaluation came across with the finding that the herbal preparation can be considered as nontoxic and animals could tolerate the extracts at doses up to 500 mg/Kg with LD50 greater than 3000 mg/Kg. It may serve as a preliminary scientific evidence for further therapeutic investigations.
Chronic inflammation is associated with various chronic illnesses including immunity disorders, cancer, neurodegeneration, and vascular diseases. Iridoids are compounds with anti-inflammatory properties. However their anti-inflammatory mechanism remains unclear. Here, we report that scropolioside B, isolated from a Tibetan medicine (Scrophularia dentata Royle ex Benth.), blocked expressions of TNF, IL-1, and IL-32 through NF-κB pathway. Scropolioside B inhibited NF-κB activity in a dose-dependent manner with IC50 values of 1.02 μmol/L. However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity. Interestingly, scropolioside B and catalpol decreased the expression of NLRP3 and cardiolipin synthetase at both the mRNA and protein level. Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol. These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.
Chronic inflammation is associated with various chronic illnesses including immunity disorders, cancer, neurodegeneration, and vascular diseases. Iridoids are compounds with anti-inflammatory properties. However their anti-inflammatory mechanism remains unclear. Here, we report that scropolioside B, isolated from a Tibetan medicine (Scrophularia dentata Royle ex Benth.), blocked expressions of TNF, IL-1, and IL-32 through NF-κB pathway. Scropolioside B inhibited NF-κB activity in a dose-dependent manner with IC50 values of 1.02 μmol/L. However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity. Interestingly, scropolioside B and catalpol decreased the expression of NLRP3 and cardiolipin synthetase at both the mRNA and protein level. Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol. These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.
Chronic inflammation is associated with various chronic illnesses including immunity disorders, cancer, neurodegeneration, and vascular diseases. Iridoids are compounds with anti-inflammatory properties. However their anti-inflammatory mechanism remains unclear. Here, we report that scropolioside B, isolated from a Tibetan medicine (Scrophularia dentata Royle ex Benth.), blocked expressions of TNF, IL-1, and IL-32 through NF-κB pathway. Scropolioside B inhibited NF-κB activity in a dose-dependent manner with IC50 values of 1.02 μmol/L. However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity. Interestingly, scropolioside B and catalpol decreased the expression of NLRP3 and cardiolipin synthetase at both the mRNA and protein level. Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol. These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.
Erigeron multiradiatus (Lindl.) Benth is a traditional Tibetan medicine herb long used to treat various diseases related to inflammation. Our previous phytochemical studies on E. multiradiatus resulted in the isolation of scutellarin, which is a known flavone glucuronide with comprehensive pharmacological actions. In present study, we investigated the inhibition action of scutellarin on high glucose-induced vascular inflammation in human endothelial cells (ECV304 cells). Consistent with previous reports, exposure of ECV304 cells to high glucose for 24 h caused an increase of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1), and promoted cell adhesion between monocyte and ECV304 cells. However, pretreatment with scutellarin (0.1 and 1 microM) reversed these effects in a concentration-dependent manner. Scutellarin was able to inhibit the activation of NF-kappaB induced by high glucose in ECV304 cells. Furthermore, although oral administration of scutellarin (10 and 50 mg/kg) did not produce significant antihyperglycemic action, it lowered the serum MCP-1 levels significantly in alloxan-induced diabetic mice. Therefore, our results suggest that scutellarin has anti-inflammation effect that may afford some protection against hyperglycemia-induced vascular inflammatory both in vitro and in vivo.
Erigeron multiradiatus (Lindl.) Benth is a traditional Tibetan medicine herb long used to treat various diseases related to inflammation. Our previous phytochemical studies on E. multiradiatus resulted in the isolation of scutellarin, which is a known flavone glucuronide with comprehensive pharmacological actions. In present study, we investigated the inhibition action of scutellarin on high glucose-induced vascular inflammation in human endothelial cells (ECV304 cells). Consistent with previous reports, exposure of ECV304 cells to high glucose for 24 h caused an increase of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1), and promoted cell adhesion between monocyte and ECV304 cells. However, pretreatment with scutellarin (0.1 and 1 microM) reversed these effects in a concentration-dependent manner. Scutellarin was able to inhibit the activation of NF-kappaB induced by high glucose in ECV304 cells. Furthermore, although oral administration of scutellarin (10 and 50 mg/kg) did not produce significant antihyperglycemic action, it lowered the serum MCP-1 levels significantly in alloxan-induced diabetic mice. Therefore, our results suggest that scutellarin has anti-inflammation effect that may afford some protection against hyperglycemia-induced vascular inflammatory both in vitro and in vivo.
BACKGROUND: Oxidative stress is concomitant with acetaminophen (APAP)-induced hepatotoxicity, which has been highlighted as therapeutic targets for such diseases. The berries of Seabuckthorn (Hippophae rhamnoides L.) have been traditionally used in Tibetan medicine for thousands of years. The effect of Seabuckthorn berry polysaccharide on drug- induced liver injury (DILI) has not yet been elucidated.PURPOSE: This study aims to investigate the protective effects and mechanisms of Seabuckthorn polysaccharide (SP) against APAP-induced hepatotoxicity.
STUDY DESIGN: Sixty C57BL/6 mice were randomly divided into six groups (n = 10 per group), namely the control group (Ctrl), APAP-induced-liver injury group (APAP), NAC pretreated group (NAC), 100 mg/kg SP pretreated group (APAP/SP100), 200 mg/kg SP pretreated group (APAP/SP200) and 200 mg/kg SP pretreated group without APAP challenge (SP200). SP was given orally to mice for 30 consecutive days prior to APAP exposure (300 mg/kg). NAC (150 mg/kg) was administrated 1 h before APAP challenge.
METHODS: ALT and AST were detected 16 h after APAP treatment; Hepatic expression of GSH, SOD, NO, iNOS and GSH-Px were examined. The expression of p-JNK, Bcl-2/Bax, p62, Keap-1 and SOD-2 was detected by Western blotting. The expression of Nrf-2 and its target genes HO-1, GCLC and NQO-1 were analyzed by RT-PCR and Western blotting.
RESULTS: Pretreatment with SP led to decreased levels of ALT and AST in APAP mice, without affecting APAP metabolism. This was accompanied by diminished liver injuries, increased levels of GSH and GSH-Px, reduced NO and iNOS expression. SP increased the activity of SOD as well as SOD-2 expression in APAP mice. SP suppressed APAP-induced JNK phosphorylation and increased the ratio of Bcl-2/Bax. Furthermore, SP decreased the expression of Keap-1 and increased the nuclear expression of Nrf-2. The expression of Nrf-2 target gene HO-1 was increased by SP pretreatment in APAP mice.
CONCLUSION: SP alleviates APAP-induced hepatotoxicity. The protective effects of SP are associated with the activation of the Nrf-2/HO-1-SOD-2 signaling pathway.
BACKGROUND: Oxidative stress is concomitant with acetaminophen (APAP)-induced hepatotoxicity, which has been highlighted as therapeutic targets for such diseases. The berries of Seabuckthorn (Hippophae rhamnoides L.) have been traditionally used in Tibetan medicine for thousands of years. The effect of Seabuckthorn berry polysaccharide on drug- induced liver injury (DILI) has not yet been elucidated. PURPOSE: This study aims to investigate the protective effects and mechanisms of Seabuckthorn polysaccharide (SP) against APAP-induced hepatotoxicity. STUDY DESIGN: Sixty C57BL/6 mice were randomly divided into six groups (n = 10 per group), namely the control group (Ctrl), APAP-induced-liver injury group (APAP), NAC pretreated group (NAC), 100 mg/kg SP pretreated group (APAP/SP100), 200 mg/kg SP pretreated group (APAP/SP200) and 200 mg/kg SP pretreated group without APAP challenge (SP200). SP was given orally to mice for 30 consecutive days prior to APAP exposure (300 mg/kg). NAC (150 mg/kg) was administrated 1 h before APAP challenge. METHODS: ALT and AST were detected 16 h after APAP treatment; Hepatic expression of GSH, SOD, NO, iNOS and GSH-Px were examined. The expression of p-JNK, Bcl-2/Bax, p62, Keap-1 and SOD-2 was detected by Western blotting. The expression of Nrf-2 and its target genes HO-1, GCLC and NQO-1 were analyzed by RT-PCR and Western blotting. RESULTS: Pretreatment with SP led to decreased levels of ALT and AST in APAP mice, without affecting APAP metabolism. This was accompanied by diminished liver injuries, increased levels of GSH and GSH-Px, reduced NO and iNOS expression. SP increased the activity of SOD as well as SOD-2 expression in APAP mice. SP suppressed APAP-induced JNK phosphorylation and increased the ratio of Bcl-2/Bax. Furthermore, SP decreased the expression of Keap-1 and increased the nuclear expression of Nrf-2. The expression of Nrf-2 target gene HO-1 was increased by SP pretreatment in APAP mice. CONCLUSION: SP alleviates APAP-induced hepatotoxicity. The protective effects of SP are associated with the activation of the Nrf-2/HO-1-SOD-2 signaling pathway.
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