Publications by authors named "Wanling Yao"

8 Publications

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Sheng Mai San ameliorated heat stress-induced liver injury via regulating energy metabolism and AMPK/Drp1-dependent autophagy process.

Phytomedicine 2021 Dec 31;97:153920. Epub 2021 Dec 31.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu 730070, China. Electronic address:

Background: Liver damage is one of the most common complications in humans and animals after heat stress (HS). Sheng Mai San (SMS), a traditional Chinese medicine prescription that originated in the Jin Dynasty, exert a therapeutic effect on HS. However, how SMS prevents liver injury after heat exposure remains unknown.

Purpose: This study aimed to investigate the pharmacological effect and molecular mechanisms of SMS on HS-induced liver injury.

Study Design: A comprehensive strategy via incorporating pharmacodynamics, targeted metabolomics, and molecular biology technology was adopted to investigate energy metabolism changes and the therapeutic mechanisms of SMS in HS-induced rat liver injury.

Methods: First, Sprague-Dawley rats were subjected to HS (38 °C/ 75% RH/ 2 h/ day) for 7 consecutive days to establish the HS model, and SMS was given orally for treatment 2 h before heat exposure. Thereafter, liver function and pathological changes in liver tissue were evaluated. Finally, the underlying mechanisms of SMS were determined using targeted energy metabolomics to comprehensively analyze the metabolic pathways and were further verified through Western-blot and qRT-PCR assays.

Results: Our results showed that SMS alleviated HS-induced liver dysfunction by reducing the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST/ALT ratios in serum and improving hepatic pathological damage. Meanwhile, SMS suppressed inflammatory response, oxidative injury, and overexpression of heat shock proteins in liver tissue after heat exposure. With the help of targeted energy metabolomics, we found that SMS could effectively regulate glycolysis and tricarboxylic acid (TCA) cycle to relieve energy metabolism disorder. Furthermore, we confirmed that SMS can facilitate the phosphorylation of AMP-activated protein kinase (AMPK) to maintain mitochondrial homeostasis through a dynamin protein 1 (Drp1)-dependent mitophagy process.

Conclusion: On the basis of energy metabolomics, the present study for the first time systematically illustrated the protective effect of SMS on HS-induced liver injury, and preliminarily confirmed that an AMPK-mediated Drp1-dependent mitophagy and mitochondria rebuilding process plays an important role in SMS intervention on HS-induced rat liver. Together, our study lends further support to the use of SMS in treating HS condition.
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http://dx.doi.org/10.1016/j.phymed.2021.153920DOI Listing
December 2021

Screening study of blood-supplementing active components in water decoction of processed with yellow rice wine based on response surface methodology.

Pharm Biol 2020 Dec;58(1):1167-1176

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, P. R. China.

Context: (Oliv.) Diels (Apiaceae) (syn. Maxim var. Oliver) processed with yellow rice wine (WAS) has a blood-supplementing effect.

Objective: To establish an optimal technology for preparing water decoction of WAS (WASD), and screen blood-supplementing fractions.

Materials And Methods: Ferulic acid and crude polysaccharide were used in optimizing the preparation technology for WASD through response surface methodology. The independent variables were liquid-solid ratio, soaking time, and extraction time. Eighty Kunming mice were randomly divided into normal control, model, and six intervention groups ( = 10). The intervention groups were given different WASD fractions by gavage (5 or 10 g/kg). The model intervention groups received acetylphenyl hydrazine (subcutaneous injection) and cyclophosphamide (intraperitoneal injection). Duration of study, 9 days. The components of blood-supplementing fractions were analyzed.

Results: The optimum extraction parameters were liquid-solid ratio, 7.69:1 mL/g; soaking time, 119.78 min; and extraction time, 143.35 min. The optimal OD value was 0.8437. RBC, WBC, and Hb in the water fraction (5, 10 g/kg) and -butanol fraction (10 g/kg) intervention groups increased significantly compared with the model group ( < 0.05). Polysaccharide and caffeic acid contents of water fraction were 252.565 and 0.346 μg/mg, respectively; ferulic acid was not detected. Caffeic acid and ferulic acid contents of -butanol fraction were 1.187 and 0.806 μg/mg, respectively, polysaccharide was not detected.

Conclusions: The optimum preparation technology of WASD was obtained, and the water, -butanol fractions were blood-supplementing fractions. This study provides a theoretical foundation for further application of WAS in the pharmaceutical industry.
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http://dx.doi.org/10.1080/13880209.2020.1844760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877401PMC
December 2020

Metabolomics study on promoting blood circulation and ameliorating blood stasis: Investigating the mechanism of Angelica sinensis and its processed products.

Biomed Chromatogr 2019 Apr 9;33(4):e4457. Epub 2019 Jan 9.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, China.

Angelica sinensis (Danggui, DG) parched with alcohol (Jiu Danggui, JDG) and charred DG are the main processed products of DG, which are used to treat blood stasis syndrome (BSS). However, their therapeutic effect and mechanisms are still unclear. Based on an acute rat BSS model, the intervention effects of DG and its processed products (DGPPs) were evaluated by the hemorheology and coagulation function parameters. Meanwhile, plasma and urine metabolites were detected and analyzed by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and multivariate statistical analysis method. The results of hemorheology, coagulation function parameters and metabolomics all showed that the BSS model was successfully established, DGPPs intervention could significantly relieve rats BSS and the therapeutic effect of JDG was best. Moreover, 23 differential metabolites (14 in plasma and nine in urine) were identified that were closely related to the BSS, involving seven potential target metabolic pathways. DGPP intervention showed different degrees of reverse effect on these metabolites. JDG was the most effective owing to extensive regulation effect on differential metabolites. This study provides a reference for understanding the pathological mechanism of BSS and the mechanism of DGPPs, which lays a theoretical foundation for the rational use of DGPPs in clinical practice.
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http://dx.doi.org/10.1002/bmc.4457DOI Listing
April 2019

Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention in acute blood stasis model rats based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Feb 2;1074-1075:51-60. Epub 2018 Jan 2.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China. Electronic address:

Taohong Siwu Decoction (TSD) is a classic prescription in traditional Chinese medicine and is widely used to promote blood circulation to remove blood stasis. However, the effect mechanisms are not yet well understood. Here, a urinary metabolomic approach based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS) was conducted to explore the changes in the endogenous metabolites and to assess the integral efficacy of TSD on acute blood stasis model rats. Then, parameters for hemorheology and coagulation functions were detected. Principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) was used to investigate the global metabolite alterations and to evaluate the preventive effects of TSD in rats. Potential metabolite markers were found using OPLS-DA and t-test. Furthermore, metabolic pathway analysis was performed to construct metabolic networks. The results showed that TSD could significantly decrease whole blood viscosity and plasma viscosity. It also significantly prolonged partial thromboplastin time (APPT) and prothrombin time (PT), increased thrombin time (TT) and lowered fibrinogen content (FIB). Moreover, 24 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees after TSD administration. In metabolic networks, amino acid metabolism (arginine and proline metabolism; histidine metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism) and lipid metabolism (glycerophospholipid metabolism; linoleic acid metabolism; alpha-linolenic acid metabolism) were closely related with the intervention mechanism of TSD on acute blood stasis. The urinary metabolomic approach can be applied to clarify the mechanism of TSD in promoting blood circulation to remove acute blood stasis and to provide the theoretical basis for further research on the therapeutic mechanism of TSD in clinical practice.
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http://dx.doi.org/10.1016/j.jchromb.2017.12.035DOI Listing
February 2018

A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of unprocessed Angelica sinensis and its 4 kinds of processed products.

J Ethnopharmacol 2018 Jan 25;211:101-116. Epub 2017 Sep 25.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China.

Ethnopharmacological Relevance: Angelica sinensis (AS), root of Angelica sinensis (Oliv.) Diels, an important kind of Chinese traditional herbal medicine, has been used for women to enrich the blood for thousands of years. It is mainly distributed in Gansu province of China. According to Traditional Chinese medicine usage, unprocessed AS (UAS) and its 4 kinds of processed products (ASs) are all used to treat different diseases or syndromes. The difference among the enriching-blood effects of ASs is unclear. And their exact mechanisms of enriching the blood are not fully understood.

Aim Of The Study: In this study, our aim is to compare the enriching-blood effect and explain the related mechanism of ASs, to lay the foundation for the blood deficiency diagnosis and the rational use of ASs in the clinic.

Materials And Methods: ASs were used to intervene the blood deficiency syndrome model mice induced by acetyl phenylhydrazine (APH) and cyclophosphamide (CTX). A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of ASs was established. The blood routine examination, ATPase, glucose-6-phosphate dehydrogenase, methemoglobin, glutathion peroxidase, glutathione reductase, and erythropoietin were measured. Two biofluids (plasma and urine) obtained from mice were analyzed with GC-MS. Distinct changes in metabolite patterns of the two biofluids after mice were induced by APH and CTX, and mice were intervened with ASs were analyzed using partial least squares-discriminant analysis. Potential biomarkers were found using a novel method including variable importance in the projection (VIP) >1.0, volcano plot analysis, and significance analysis of microarray.

Results: The results of hematological, biochemical parameters and the integrated metabolomics all showed the blood deficiency syndrome model was built successfully, ASs exhibited different degree of enriching-blood effect, and AS pached with alcohol (AAS) exhibited the best enriching-blood effect. 16 metabolites in the plasma and 8 metabolites in the urine were considered as the potential biomarkers. These metabolites were involved in 7 metabolic pathways which were concerned with the different enriching-blood effect mechanisms of ASs. The correlation analysis results confirmed L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine) and Cholesterol (urine) were strong positive or negative associated with biochemical indicators.

Conclusions: The enriching-blood effects of ASs are different. The pathological mechanisms of blood deficiency syndrome and the enriching-blood effect mechanism of ASs are involved in 7 metabolic pathways. L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine), Cholesterol (urine) are four important biomarkers being related to the enriching-blood effect of ASs. The combination of VIP, volcano plot analysis and significance analysis of microarray is suitable for screening biomarkers in metabolomics study. They can lay the foundation for clinical practice.
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http://dx.doi.org/10.1016/j.jep.2017.09.028DOI Listing
January 2018

Treatment effects and mechanisms of Yujin Powder on rat model of large intestine dampness-heat syndrome.

J Ethnopharmacol 2017 Apr 19;202:265-280. Epub 2017 Mar 19.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China. Electronic address:

Ethnopharmacological Relevance: Yujin Powder (YJP), an old prescription, is one of the most classical prescription for treating the large intestine dampness-heat syndrome (LIDHS). However, its potential modern pharmacological mechanisms remain unclear.

Aim Of The Study: The present study was designed to explore the essence of LIDHS and treatment mechanisms of the YJP on the LIDHS.

Methods: The rat model of LIDHS was established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment (HTHE), drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of LIDHS. Then the clinical symptoms and signs, blood routine, blood biochemistry, whole blood viscosity (WBV), serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed, respectively.

Results: The results showed that the clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of LIDHS, moreover, there were obvious systemic inflammatory response and extensive congestion. And after treatment with YJP in different dosages, the clinical symptoms and signs of the rats with LIDHS were improved; the indexes of blood routine and blood biochemistry and inflammatory cytokines levels tended to be normal; the WBV decreased and histopathological changes of major organs were alleviated or returned to normal. There was an obvious dose-effect relationship, and the high dose of YJP (HD-YJP) had the best treatment effects.

Conclusions: These results suggested that in LIDHS, diarrhea was the major clinical manifestation; the large intestine was the main lesion area; mucosa injury, inflammation and congestion of the large intestine with systemic inflammatory response and congestion were the most typical pathological characteristics. Meanwhile, YJP exhibited the comprehensive effects of anti-diarrhea, anti-inflammation, lowering blood lipid, relieving blood stasis, repairing intestinal mucosa and regulation and protection of multiple organs on LIDHS. These findings provided not only important information for understanding the essence of LIDHS but also the theoretical basis for developing new-drugs for treating dampness-heat type of diarrheal diseases.
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http://dx.doi.org/10.1016/j.jep.2017.03.030DOI Listing
April 2017

Effects of volatile oils of Angelica sinensis on an acute inflammation rat model.

Pharm Biol 2016 Sep 6;54(9):1881-90. Epub 2016 Feb 6.

a College of Veterinary Medicine, Gansu Agricultural University , Lanzhou , Gansu Province , People's Republic of China.

Context Despite several pharmacological studies of volatile oils of Angelica sinensis (Oliv.) Diels (Umbelliferae) (VOAS), its anti-inflammatory mechanism remains unknown. Objective The study investigates the effects of VOAS on the lipopolysaccharide (LPS)-induced acute inflammation rat model and analyzes its possible anti-inflammatory mechanisms. Materials and methods Fourty rats were randomly divided into the control, model, VOAS and dexamethasone (Dex) groups. The VOAS and Dex groups were given VOAS (0.176 mL/kg) and Dex (40 μg/kg), respectively. Rats in all groups except the control group were intraperitoneally injected with LPS (100 μg/kg), their exterior behaviour and liver pathological changes were observed, and the level of white blood cell (WBC), the number of neutrophils (NE)%, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), tumour necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, IL-10, histamine (HIS), 5-hydroxytryptamine (5-HT), nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were detected. Results Compared with the model group, VOAS and Dex significantly accelerated the recovery of the exterior behaviour, the liver pathological changes of rats, and increased the level of IL-10, but decreased the level of WBC, NE%, GOT, GPT, ALP, TNF-α, IL-1β, IL-6, HIS, 5-HT, NO, PGE2, iNOS and COX-2 (p < 0.05). Conclusion VOAS exhibits anti-inflammatory and liver protection effects by inhibiting the secretion of the pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), the inflammatory mediators (HIS, 5-HT, PGE2 and NO), the inflammation-related enzymes (iNOS and COX-2), as well as promoting the production of the anti-inflammatory cytokines IL-10.
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http://dx.doi.org/10.3109/13880209.2015.1133660DOI Listing
September 2016

The investigation of anti-inflammatory activity of volatile oil of Angelica sinensis by plasma metabolomics approach.

Int Immunopharmacol 2015 Dec 11;29(2):269-277. Epub 2015 Nov 11.

Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China. Electronic address:

Angelica sinensis (AS) is an important medicinal plant, and volatile oil is the main pharmacologically active ingredient. This study was aimed to investigate the anti-inflammatory activity of the volatile oil of A. sinensis (VOAS) and explore its potential anti-inflammatory mechanism by plasma metabolomics approach. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Paw edema, histamine (HIS) and 5-hydroxytryptamine (5-HT) were detected. Then, we analyzed plasma metabolic profiling of acute inflammation and performed pathway analysis on the metabolite markers reversed after VOAS administration and further integration of metabolic networks. The results showed that VOAS could alleviate the paw edema and decrease plasma HIS and 5-HT levels. Fourteen metabolite markers of acute inflammation were screened, and the levels were all reversed to different degrees after VOAS administration. These metabolite markers mainly related to linoleic acid metabolism, ascorbate and aldarate metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine and threonine metabolism. In metabolic networks, glycine and arachidonic acid were node molecules. It indicated that VOAS could significantly inhibit systemic inflammatory response triggered by acute local stimulation and it exerted anti-inflammatory activity mainly through regulating the disturbed metabolic networks centered on glycine and arachidonic acid.
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http://dx.doi.org/10.1016/j.intimp.2015.11.006DOI Listing
December 2015
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