Protective role of fruits of Rosa odorata var. gigantea against WIRS-induced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis.

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea (FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress (WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved. Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin (H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot. Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) contents; anti-inflammatory cytokines interleukin-10 (IL-10) and prostaglandin E2 (PGE2) levels as well as regulatory factors tumor necrosis factor-α (TGF-α) and somatostatin (SS) contents, while decreasing malondialdehyde (MDA), nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), gastrin (GAS) and endothelin (ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen (PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-κB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival. Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

Control Effects of Short-Term Heatwaves on a Holocyclic Aphid.

The soybean aphid, A. glycines, is an important soybean pest. Harbin, in the Heilongjiang Province, is an area with increasing temperatures in China that faces frequent short-term heatwaves. In this study, the development, reproduction, and morph differentiation of A. glycines have been studied when they were exposed to diurnal at 35 °C for seven days, beginning at different developmental stages. The nymph stage duration of A. glycines was longer, the adult lifespans and total lifespans were shorter, and their bodies were smaller when exposed to a diurnal of 35 °C beginning at the 1st to 4th stadium. The adult reproduction period was shorter, and the adult fecundity and intrinsic rate of increase were smaller than those of aphids reared at a diurnal of 25 °C. A higher and lower proportion of gynoparae and males were deposited as offspring on day 13 by adults when exposed to diurnal at 35 °C, beginning at the 1st to 4th stadium, respectively, than those of aphids reared at a constant of 20 °C. These results are important for predicting the dynamics of A. glycines in Harbin soybeans. This provides evidence that short-term heatwaves are probably useful for controlling A. glycines, by inhibiting development and male morphogenesis.

Effects of heat wave on development, reproduction, and morph differentiation of Aphis glycines (Hemiptera: Aphididae).

As global warming intensifies, heat waves occur frequently in the summer and autumn in Heilongjiang Province, northeast China. The soybean aphid, Aphis glycines Matsumura, is an important pest of soybean in the region, which faces great survival pressure due to high temperature. In this study, A. glycines fed soybean (AgFS) and wild soybean (AgFW) were exposed to diurnal 35 °C for 7 days begin at different developmental stages, and the development, reproduction, and morph differentiation were studied. When AgFS were exposed to heat waves from the second stadium to the adult stage, they performed worse in adult lifespan and fecundity than the control. When AgFW were exposed to heat waves begin at different developmental stages, the adult lifespan and reproduction period were shortened and reproduction ability decreased. When exposed to heat waves, the adult fecundity and intrinsic rate of increase in AgFW were lower than those of AgFS. Lower proportion of males were deposited on day 13, when AgFS and AgFW were exposed to diurnal 35 °C begin at different developmental stages. The results showed that heat waves lasting for 7 days were likely to be useful in the management of A. glycines, which reduced adult reproduction ability and male differentiation proportion in the offspring and significantly affected AgFW compared to AgFS. These results are important for predicting the dynamics of A. glycines in Heilongjiang, northeast China, where the local environmental temperature is increasing and heat waves occur frequently.

Identification of chemical constituents of Qingjin Yiqi granules and comparative study on pharmacokinetics of 23 main bioactive components in normal and Lung-Qi deficiency rats by UPLC-MS/MS method.

Qingjin Yiqi granules (QJYQ granules) are hospital preparations derived from ancient prescriptions under the guidance of academician Zhang Boli; they have the effect of invigorating qi and nourishing yin, strengthening the spleen and harmonizing the middle, clearing heat, and drying dampness, and are mainly used for patients with coronavirus disease 2019 (COVID-19) during the recovery period. However, their chemical constituents and pharmacokinetic characteristics in vivo have not been systematically investigated. In this study, 110 chemical constituents of QJYQ granules were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and a fast and sensitive ultra-high-performance liquid chromatography-mass spectrometry method was developed and validated for the target analytes. A rat model of lung-qi deficiency was established by subjecting mice to passive smoking combined with cold baths, and 23 main bioactive components of QJYQ granules were analyzed in normal and model rats after oral administration. The results showed that, compared to the normal group, there were significant differences in the pharmacokinetics of baicalin, schisandrin, ginsenoside Rb1, naringin, hesperidin, liquiritin, liquiritigenin, glycyrrhizic acid, and hastatoside in the model rats (P < 0.05), indicating that the in vivo processes of the above components changed under pathological conditions, suggesting that they may have pharmacological effects as active components. This study has helped identify QJYQ particulate substances and further supports their clinical application..

Licochalcone A inhibits the assembly function of ß-barrel assembly machinery in Escherichia coli.

Antimicrobial resistance (AMR) crisis urges the development of new antibiotics. In the present work, we for the first time used bio-affinity ultrafiltration combined with HPLC-MS (UF-HPLC-MS) to examine the interaction between the outer membrane ß-barrel proteins and natural products. Our results showed that natural product licochalcone A from licorice interacts with BamA and BamD with the enrichment factor of 6.38 ± 1.46 and 4.80 ± 1.23, respectively. The interaction was further confirmed by use of biacore analysis, which demonstrated that the Kd value between BamA/D and licochalcone was 6.63/28.27 µM, suggesting a good affinity. To examine the effect of licochalcone A on BamA/D function, the developed versatile in vitro reconstitution assay was used and the results showed that 128 µg/mL licochalcone A could reduce the outer membrane protein A integration efficiency to 20%. Although licochalcone A alone can not inhibit the growth of E. coli, but it can affect the membrane permeability, suggesting that licochalcone A holds the potential to be used as a sensitizer to combat AMR.

Ethnopharmacology, phytochemistry and pharmacology of Benincasae Exocarpium: A review.

Benincasae Exocarpium (BE, Dongguapi in Chinese), as the dried outer pericarp of Benincasa hispida (wax gourd) in Cucurbitaceae family, is one of traditional Chinese medicines with the same origin as medicine and food. Up to now, 43 compounds were isolated from BE, including flavonoids, alkaloids, tannins, phenolic acids, soluble fiber and carbohydrates. Modern pharmacological studies and clinical practice showed that BE has diuretic, hypolipidemic effects, hypoglycemic, antioxidant, antibacterial, and other effects. The folk uses, functional factors, pharmacological activities, patents and clinical applications of BE were reviewed in this paper. In addition, the paper also discussed the current problems for the further studies. The information summarized in this paper provides valuable clues for the comprehensive utilization of medicine and food resources and gives a scientific basis for the development of medicinal plants of BE.

Established UPLC-MS/MS procedure for multicomponent quantitative analysis of rat plasma: Pharmacokinetics of Taohong Siwu Decoction in normal and acute blood stasis models.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of China's 100 classic recipes, Taohong Siwu Decoction (THSWD) consists of Siwu Tang flavored peach kernel and safflower, and is used to nourish and activate blood. Accordingly, THSWD is mainly administered to treat blood deficiency and stasis syndrome. According to prior studies, THSWD induces antioxidant stress, inhibits inflammatory reactions, inhibits platelet aggregation, prevents fibrosis, reduces blood lipids, prolongs clotting time, prevents atherosclerosis and vascular pathology, improves hemorheological changes, and regulates related signaling pathways. MATERIALS AND METHODS: A sensitive analytical method was developed to detect the marker components of THSWD using UPLC-Q-TOF-MS. A rapid and sensitive UPLC-MS/MS analytical method was developed and applied to detect 16 major bioactive components in normal and acute blood stasis (ABS) rats following oral administration of THSWD. The metabolic process of THSWD in vivo was evaluated and the differences in pharmacokinetic parameters between the normal and ABS rat metabolic processes were compared. RESULTS: This method was fully validated based on its excellent linearity (r2 < 0.99), satisfactory intra- and inter-day precisions (RSD <15%), and good accuracy (RE within ±14.83%). The stability, matrix effects, and extraction recoveries of the rat plasma samples were also within the acceptable limits (RSD <15%). Compared to normal rats, the pharmacokinetics of the major active constituents (except Senkyunolide G) were significantly different (P < 0.05) in the ABS model rats, indicating that the metabolism of the 16 compounds in vivo may change under disease conditions. CONCLUSIONS: In this study, a sensitive UPLC-Q-TOF-MS method was established to analyze the main components of THSWD, and a UPLC-MS/MS analytical method was developed and applied for the pharmacokinetic parameter detection of the 16 main bioactive components in normal and ABS rats. Our findings lay the foundation for further studies on the pharmacokinetic-pharmacodynamic correlation for THSWD.

Formulation of Aucklandiae Radix Extract-Loaded Nanoemulsions and Its Characterization and Evaluations In Vitro and In Vivo.

This study aimed to screen, design, and evaluate an optimal nanoemulsion formulation for Aucklandiae Radix extraction (ARE). A simple lattice design (SLD) method was used to determine the preparation process of Aucklandiae Radix extract-nanoemulsions (ARE-NEs). After optimization, the average particle size of ARE-NEs was 14.1 ± 1.1 nm, polydispersity index was 0.2376, and pH was 6.92. In vitro penetration tests verified that the permeability ratios of costunolide (CE), dehydrocostus lactone (DE), and ARE-NEs were approximately 6.33 times and 8.20 times higher, respectively, than those of the control group. The results of the pharmacokinetic study indicated that after topical administration, the content of the index components of ARE-NEs increased in vivo, with a longer release time and higher bioavailability in vivo than in vitro. The index components were CE and DE, respectively. In addition, a skin irritation test was conducted on normal and skin-damaged rabbits, aided by HE staining and scanning electron microscopy, to reveal the transdermal mechanism of ARE-NEs and proved that NEs are safe for topical application. ARE-NEs energetically developed the properties of skin and penetration through the transdermal route, which were secure when applied via the transdermal delivery system .

Xuanfei Baidu Formula attenuates LPS-induced acute lung injury by inhibiting the NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is a common manifestation of COVID-19. Xuanfei Baidu Formula(XFBD) is used in China to treat mild or common damp-toxin obstructive pulmonary syndrome in COVID-19 patients. However, the active ingredients of XFBD have not been extensively studied, and its mechanism of action in the treatment of ALI is not well understood. AIM OF THE STUDY: The purpose of this study was to investigate the mechanism of action of XFBD in treating ALI in rats, by evaluating its active components. MATERIALS AND METHODS: Firstly, the chemical composition of XFBD was identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The potential targets of XFBD for ALI treatment were predicted using network pharmacological analysis. Finally, the molecular mechanism of XFBD was validated using a RAW264.7 cell inflammation model and a mouse ALI model. RESULTS: A total of 113 compounds were identified in XFBD. Network pharmacology revealed 34 hub targets between the 113 compounds and ALI. The results of Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses indicated that the NF-κB signaling pathway was the main pathway for XFBD in the treatment of ALI. We found that XFBD reduced proinflammatory factor levels in LPS-induced cellular models. By examining the lung wet/dry weight ratio and pathological sections in vivo, XFBD was found that XFBD could alleviate ALI. Immunohistochemistry results showed that XFBD inhibited ALI-induced increases in p-IKK, p-NF-κB p65, and iNOS proteins. In vitro experiments demonstrated that XFBD inhibited LPS-induced activation of the NF-κB pathway. CONCLUSION: This study identified the potential practical components of XFBD, combined with network pharmacology and experimental validation to demonstrate that XFBD can alleviate lung injury caused by ALI by inhibiting the NF-κB signaling pathway.

The protective effect of quinoa on the gastric mucosal injury induced by absolute ethanol.

BACKGROUND: Gastric mucosal injury caused by ethanol is a common gastrointestinal disease. Quinoa (Chenopodium quinoa Willd.), as a nutrient-rich grain, plays a significant role in preventing and treating gastric mucosal damage. The present study aimed to explore the protective effect of quinoa on alcohol-induced gastric mucosal damage and its possible mechanism. RESULTS: The ethanol-induced gastric mucosal injury rat model was used for in vivo experiments and H2 O2 -induced GES-1 cells for in vitro experiments to elucidate the protective effect of quinoa. The results show that quinoa water extract can increase the superoxide dismutase level and decrease the malondialdehyde level in vitro and in vivo. Furthermore, quinoa also reduced the bleeding point and bleeding area in rats with ethanol-induced gastric mucosal injury and improved gastric histopathological changes. H2 O2 significantly increased the levels of inflammatory factors in GES-1 cells, which were markedly ameliorated by quinoa water extract. Likewise, quinoa water extract regulated the protein expression levels of Nrf2, Keap1, HO-1, p-IKK, and p-NF-κB through Nrf2 and nuclear factor-κB signaling pathways, reducing the production of oxidative stress and inflammation, thereby repairing the damaged gastric mucosa. CONCLUSION: The findings of this study demonstrated that quinoa shows protective effect against ethanol-induced gastric mucosal injury through its anti-inflammatory and anti-oxidant effects. We propose that our research will provide a reference for quinoa as a functional food. © 2022 Society of Chemical Industry.

Sericic Acid Ameliorates DSS-induced Ulcerative Colitis in Mice by Modulating the NF-κB and Nrf2 Pathways.

BACKGROUND: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease. In previous studies, we found extracts from the roots of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils have a therapeutic effect on UC. Furthermore, sericic acid (SA) is a pentacyclic triterpenoid isolated from this plant that is being used for the first time. The purpose of this study was to investigate whether SA has anti-inflammatory and therapeutic effects on UC and its underlying mechanisms. METHODS: In this study, we used a dextran sulfate-induced UC mouse model and lipopolysaccharide (LPS)-induced inflammatory cell model along with an enzyme-linked immunosorbent assay (ELISA) to quantify the abundance of inflammatory factors and oxidative stress factors in tissues and cells. HE staining was used to analyze the therapeutic effect of the drugs on the UC mouse model. The expression levels of oxidative stress-related proteins were detected using immunoblotting and immunohistochemistry. The anti-inflammatory targets of SA were screened using protein chip arrays and verified by immunoblotting. RESULTS: We found that SA had anti-inflammatory and antioxidant effects in animal and cellular inflammation models. SA inhibited the levels of NO, TNF-α, IL-6, IL-1ß, and MDA in tissues and cells and upregulated the expression level of SOD. Animal experiments showed that SA alleviated the shortening of colon length and colon pathological damage caused by DSS. The antiinflammatory targets of SA were screened using protein chip arrays, and SA was found to inhibit proteins related to the NF-κB signaling pathway. Finally, immunoblotting and immunohistochemistry showed that SA downregulated the expression of p-IKKα/ß and its downstream protein p-NF-κB, while promoting the expression of Nrf2 and its downstream protein HO-1. CONCLUSION: The above results indicated that SA alleviated DSS-induced colitis by inhibiting NF-κB signaling pathway and activating Nrf2 pathway.

Adaptability of Two Soybean Aphid Species to High Diurnal Temperatures.

The local temperature in the Harbin region of northeast China has been rising, with temperatures above 27°C often being recorded. The soybean aphid, Aphis glycines (Matsumura) (Hemiptera: Aphididae), and foxglove aphid, Aulacorthum solani (Kaltenbach) (Hemiptera: Aphididae), are important pests in soybeans in the region, which face great survival pressure due to rising temperatures. In this study, A. glycines and A. solani were reared at thermoperiods with diurnal temperatures of 25, 27, 29, 31, 33, 35, and 37°C, nocturnal temperature of 20 °C, 70% ±â€…5% relative humidity, and a photoperiod of 14:10 (L: D) hr. Diurnal thermoperiod 25°C was used as control. Some life characteristics of the aphids were assessed. The adaptation of A. solani to high diurnal temperatures was found to be worse than that of A. glycines. Aphis glycines could develop and reproduce successfully at diurnal temperatures of 27-35°C, whereas A. solani could only develop and reproduce at 27-29°C. At diurnal thermoperiods at 25°C, adult lifespan of A. solani was as long as that of A. glycines. When diurnal temperatures increased from 27 to 31°C, adult lifespan of A. solani were shorter than those of A. glycines. At diurnal thermoperiods at 25 and 27°C, the body sizes of A. solani adults were larger than those of A. glycines. At diurnal thermoperiods at 29 and 31°C, the body size of A. solani adults were as large as those of A. glycines. Our results provide important information on the survival, development, and reproduction of A. glycines and A. solani exposed to temperatures above 27°C, which is important for evaluating the adaptability of aphids to high temperatures and predicting their dynamics in soybeans in northeast China, where the local environmental temperature continues to rise.

Chemical constituents and pharmacological activities of medicinal plants from Rosa genus.

The genus Rosa (Rosaceae family) includes about 200 species spread in the world, and this genus shows unique advantages in medicine and food. To date, several scholars concentrated on compounds belonging to flavonoids, triterpenes, tannins, polysaccharide, phenolic acids, fatty acids, organic acids, carotenoids, and vitamins. Pharmacological effects such as antineoplastic and anti-cancer properties, anti-inflammatory, antioxidant, liver protection, regulate blood sugar, antimicrobial activity, antiviral activity, as well as nervous system protection and cardiovascular protection were wildly reported. This article reviews the chemical constituents, pharmacological effects, applications and safety evaluations of Rosa plants, which provides a reference for the comprehensive utilization of medicine and food resources and gives a scientific basis for the development of medicinal plants of the genus Rosa.

Regulatory effect of traditional Chinese medicines on signaling pathways of process from chronic atrophic gastritis to gastric cancer.

Chronic atrophic gastritis (CAG), a common disease of digestive system, is an extremely important cause of gastric cancer (GC). The occurrence and development of CAG involves the abnormality of multiple signaling pathways. Traditional Chinese medicines (TCMs) has the advantages of mild action, multi-target and small adverse reaction, etc., which broadens the way for the treatment of the disease, and TCMs can play a therapeutic role by regulating multiple signaling pathways. In this review, based on the related experiments of TCMs and Chinese herbal compounds in recent years, the related literatures were searched and 10 kinds of signaling pathways involved were summarized, in order to provide a reference for further research on reversing or delaying the progress of CAG and preventing gastric cancer.

Protective Effects of Grape Seed Proanthocyanidin Extract in Preventing DSS Induced Ulcerative Colitis Based on Pharmacodynamic, Pharmacokinetic and Tissue Distribution.

BACKGROUND: Based on pharmacodynamic, pharmacokinetic and tissue distribution studies, we explored the potential effect of grape seed proanthocyanidin extract (GSPE) on dextran sodium sulfate (DSS) -induced ulcerative colitis in mice and its underlying mechanism. METHODS: A liquid chromatography-mass spectrometry method was developed to measure the content of five components of GSPE in rat plasma and tissue. After oral administration of GSPE, correlative index levels of interleukin- 1ß (IL-1ß), interleukin-6 (IL-6), factor-α (TNF-α), Nitric Oxide (NO), malonaldehyde (MDA), and superoxide dismutase (SOD) were detected in the serum and colon tissues. The protein expression levels of HO-1, Nrf2 and NF-κB in the mouse colonic mucosa were analysed using immunohistochemistry. RESULTS: Pharmacodynamic tests showed substantially reduced mice body weight, diarrhea, and bloody stool in the model group. The pathological damage to the colonic mucosa of mice in the GSPE groups was remarkably reduced in a dose-dependent manner. The histopathological score of the colon in the model group was significantly higher than that of the control group (P <0.05), suggesting that DSS caused severe damage to the colon. After oral administration of GSPE, the serum and colonic tissue levels of IL-1ß, IL-6, TNF-α, NO, and MDA decreased, whereas SOD content increased. Moreover, the protein levels of NF-κB and Keap-1 were significantly decreased, whereas the expression levels of Nrf2 and HO-1 proteins increased (P<0.01) based on the results of the microwaveimmunohistochemical assay. The pharmacokinetic results showed that catechin, epicatechin, and procyanidins B1, B2, and B4 are widely distributed in the tissues and blood of rats and may accumulate in some tissues. Catechin and epicatechin peaked at 0.25 and 1.5 h for the first and second time, respectively. Procyanidin B1, B2, and B4 peaked at 0.5 and 1.5 h for the first and second time, respectively, owing to the effect of the hepato-enteric circulation. The active components of GSPE can reach the colon of the lesion site, and hepatoenteric circulation can increase the residence time of the active components in the body, further increasing the anti-ulcer activity. CONCLUSION: Our findings suggest that GSPE has a potential protective effect against DSS-induced ulcerative colitis in mice.

Comparative pharmacokinetics of 24 major bioactive components in normal and ARDS rats after oral administration of Xuanfei Baidu granules.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu prescription, consisting of 13 Chinese medicines, was formulated by academicians Boli Zhang and Professor Qingquan Liu based on their experience in first-line clinical treatment of COVID-19. Xuanfei Baidu granules (XFBD granules) are a proprietary Chinese medicine preparation developed based on Xuanfei Baidu prescription. It is recommended for the treatment of patients with the common wet toxin and lung stagnation syndrome of COVID-19. However, the pharmacokinetic characteristics of its major bioactive components in rats under different physiological and pathological conditions are unclear. MATERIALS AND METHODS: A rapid and sensitive analytical method, ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS), was developed and applied to 24 major bioactive components in normal and ARDS rats after oral administration of XFBD granules. We studied the metabolic process of XFBD granules in vivo to compare the differences in pharmacokinetic parameters between normal and model metabolic processes. RESULTS: This method was successfully applied to the pharmacokinetic investigation of 24 major components of XFBD granules following oral administration in normal and ARDS rats. Eight components, including ephedrine and amygdalin, were more highly absorbed and had shorter Tmax values than the model group; the absorption of six components, such as rhein, decreased in ARDS rats, and there was no significant difference in the absorption of ten components, such as verbenalin and naringin, between the normal and ARDS rats. The results showed that the peak times of other analytes were very short, and 80% of these target constituents were eliminated in both normal and ARDS rats within 6 h except for liquiritigenin and 18ß-glycyrrhetinic acid. CONCLUSIONS: In this study, a rapid and sensitive UPLC-MS/MS analytical method was developed and applied to 24 major bioactive components in normal and ARDS rats after the oral administration of XFBD granules. This will serve to form the basis for further studies on the pharmacokinetic-pharmacodynamic correlation of XFBD granules.

Development and Validation of a Sensitive UPLC-Q-TOF-MS/MS for the Measurement of Nine Components in Rat Plasma and Tissues and its Application to Pharmacokinetics and Tissue Distribution Studies with Xuanfei Baidu Granules.

BACKGROUND: Xuanfei Baidu granules (XFBD granules) are based on the prescription of Xuanfei Baidu, which showed promise as a first-line treatment against Corona Virus Disease 2019 (COVID-19) in Wuhan, Hubei. On March 2, 2021, XFBD granules were marketed as a novel drug for epidemic diseases. However, there is little information about the pharmacokinetics and tissue distribution of the main constituents in XFBD granules. METHODS: A sensitive analytical method was developed for detecting the marker components of XFBD granules by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOFMS/ MS), and for studying its pharmacokinetics and tissue distribution by UPLC-QDa. RESULTS: Following an oral administration of a single granule in experimental rats at a dose of 14 g/kg for pharmacokinetic and tissue distribution studies, 42 compounds and nine analytes were identified in XFBD granules. Nine compounds were detected in the lungs and the liver of the rats. Six compounds were detected in the kidneys. Five compounds were detected in the spleen and three were detected in the heart. As it went undetected in the brain, XFBD granules are considered unable to cross the blood-brain barrier. CONCLUSION: A sensitive UPLC-Q-TOF-MS/MS method was established and validated for the quantification of nine components in rat plasma and tissue samples. This method was successfully applied to study the pharmacokinetics and tissue distribution profiles of XFBD granules after their oral administration.

Effectiveness of the fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils in the protection and the healing of ethanol-induced rat gastric mucosa ulcer based on Nrf2/NF-κB pathway regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils (Rosaceae), is also known as "GU-GONG-GUO", the root of which has been recognized as common ethnodrug from the Yi nationality for treating inflammatory bowel disease. The aim of the present study was to investigate the preventive and curative effects of extract from the fruits of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils (FOE) in vitro and in vivo as well as elucidate the potential mechanisms of the action involved. MATERIALS AND METHODS: Male Wistar rats were applied to ethanol-induced gastric ulcer model. They were divided into six groups: control, model (GU), positive (Magnesium aluminate chewable tablets, 125 mg/kg), FOE low (125 mg/kg), middle (250 mg/kg) and high (500 mg/kg) doses groups. Histopathology observation of gastric tissues was detected by hematoxylin and eosin (H&E) staining. The expression of Nrf2, HO-1, Keap1, NF-κB p65 and IKKα/ß in gastric tissues were evaluated by immunohistochemistry (IHC). The levels of cytokines in serum and tissues were measured by Enzyme-linked immunosorbent assay (ELISA). The expression of Nrf2, HO-1, Keap1, NF-κB p65, IKKα/ß, PCNA and COX2 proteins were ulteriorly assessed by Western blotting to elucidate the molecular mechanism of FOE's protective effect on gastric ulcer. RESULTS: MTT detection showed that LPS reduced RAW264.7 cell survival, and FOE blocked the inhibition of RAW264.7 cell growth induced by LPS. When RAW264.7 cells were treated with both FOE (100 µg mL-1) and LPS (5 µg mL-1) for 24 h, compared with the model group, the level of NO, TNF-α, IL-6, IL-1ß and MDA significantly decreased, and the activity of SOD was significantly reduced. Obvious pathological injuries in the GU model group were observed, which was improved after treatments with FOE. The contents of pro-inflammatory factors in serum and tissues were decreased by 25% whereas prostaglandin E2 (PGE2) and epidermal growth factor (EGF) were increased by 30% in a dose-dependent manner after FOE (500 mg/kg) treatments. In addition to the promotion effects of superoxide dismutase (SOD), FOE (500 mg/kg) also attenuated the levels of nitric oxide (NO) and malondialdehyde (MDA) by 20%. Likewise, the expression of NF-κB p65, IKKα/ß and Keap1 were suppressed after treatments with FOE whereas Nrf2 and HO-1 showed the opposite trend, which mechanisms were found to be associated with Nrf2/NF-κB signaling pathways. CONCLUSION: The study demonstrated that FOE is able to protect against GU via inhibiting NF-κB signaling pathway and activating Nrf2 signaling pathway, which might provide a stronger theoretical basis for the treatment of GU.

Sesquiterpene lactones of Aucklandia lappa: Pharmacology, pharmacokinetics, toxicity, and structure-activity relationship.

The medicinal part of Aucklandia lappa (Asteraceae) is its dried root, which is one of the commonly used Chinese medicinal materials. Here we reviewed sesquiterpene lactones isolated from A. lappa over the past ten years in the following aspects of pharmacological activities, pharmacokinetics, toxicology, structure-activity relationship. Pharmacological activities consist of anti-cancer, anti-inflammatory activity, anti-immunity activity, anti-oxidant activity, antimicrobial activity, spasmolytic activity and so on. The extractive, showing similar pharmacokinetics parameters, may exert their various biological activities by the interaction of their α-methylene-γ-butyrolactone moiety with the thiol groups of biomacromolecules through Michael-addition. However, the poor aqueous solubility, non-selective binding as a Michael acceptor at undesired targets limited clinical translation of this class. In order to evaluate the potential effect of the extractive applied in clinical trial, the present review outlines information on pharmacological activities, pharmacokinetics, toxicology, and structure-activity relationship, as well as the future research directions of the extractive for further development and utilization of A. lappa.

Purification and identification of buckwheat hull flavonoids and its comparative evaluation on antioxidant and cytoprotective activity in vitro.

Buckwheat hulls, by-products of buckwheat processing, contain various flavonoids, but the antioxidant capacity and synergy of different flavonoids are unclear. The purpose of this study was to evaluate the antioxidant activity of flavonoid monomers and high-flavonoid component (HBHF) in buckwheat hulls using chemical-based assays and cellular-based assays. Four kinds of flavonoids were identified as rutin, isoorientin, vitexin, and hyperoside from buckwheat hulls. In chemical-based assays, rutin and HBHF showed relatively high free radical scavenging activities and total antioxidant capacities. In cellular-based assays, however, HBHF showed much higher proliferation activity against cell damage than flavonoid monomers when HepG2 cell was oxidatively damaged by H2O2 or high glucose. The cytoprotective activities of flavonoid monomers and HBHF were closely associated with reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA) or increasing catalase (CAT) activity. In conclusion, buckwheat hull flavonoids are the favorable application candidates for natural antioxidants.