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  • Yan HAI, Ning DING, Ze-kun ZHANG, Bei-bei ZHANG, Yu DU, Xiao-xue ZHANG, Na LI, Xiang-yu GE, Bo-wen GAO, She-po SHI
    Acta Pharmaceutica Sinica. 2022, 57(8): 2423-2429.

    Cytochrome P450 reductase (CPR) is essential for the electron transport chain of cytochrome P450s, playing an indispensable role in electron transfer in vivo. In this study, one cDNA encoding cytochrome P450 reductase (Ascpr1) was identified from the callus of Aquilaria sinensis. Ascpr1 contains an open reading frame of 2 124 bp. The deduced protein is composed of 707 amino acids, with a predicted molecular weight of 78.82 kD. Phylogenetic analysis revealed that AsCPR1 is a type Ⅱ CPR protein closely related to the CPR from Theobroma cacao. Transmembrane prediction using TMHMM 2.0 indicated that the amino acids 52-71 of AsCPR1 comprise a transmembrane region. After truncating of 67 amino acid residues from N-terminal, the truncated AsCPR1 was successfully expressed in E. coli Transetta (DE3). Further purification of the recombinant AsCPR1 by affinity chromatography and determination of the enzymatic activity allowed the reducing ability of AsCPR1 to cytochrome C in vitro. The results pave the way for further study on the synthesis of defensive chemicals involved in P450s and the functions of CPR in self-defense of A. sinensis.

  • Chen LIU, Cheng-gen ZHU, Cheng-bo XU, Bin MU, Qing-lan GUO, Jian-gong SHI
    Acta Pharmaceutica Sinica. 2022, 57(8): 2405-2415.

    Eleven monoterpene glucosides were isolated from a water decoction of Monochasma savatieri by column chromatography over macroporous adsorbent resin, MCI resin, Sephadex LH-20, and HW-40C, combined with preparative TLC, reversed phase HPLC, and flash column chromatographic techniques. Their structures were elucidated by comprehensive analysis of spectroscopic data, along with acidic and enzymatic hydrolysis as well as electronic circular dichroism (ECD) and NMR calculations, including six new compounds (1-4, 7 and 8), named monochasides A-D, G and H, respectively. Comparing the reported data of 9-hydroxylinaloyl 3-O-β-D-glucoside (5), (6Z)-9-hydroxylinaloyl 3-O-β-D-glucoside (6), and kankanoside D1 (9) with those obtained in this study, the absolute configurations of 6 and 9 were proved for the first time. Other two compounds were identified as 8-hydroxygeraniol 1-O-β-D-glucopyranoside (10) and 8-hydroxygeraniol 8-O-β-D-glucopyranoside (11), respectively.

  • Xian-yun FU, Ping MAO, Yong-li YI, Pei-pei CHEN, Zhao QU
    Acta Pharmaceutica Sinica. 2022, 57(8): 2494-2502.

    This paper aims to investigate the regulatory mechanism of blood-activating and stasis-dissipating drugs on fecal metabolic characteristics of rhubarb-peach kernel in mice with adenomyosis (AM) using fecal metabolome method. Adenomyosis was modeled by pituitary transplantation, and after the end of modeling administration, fecal samples were collected from mice. Non-targeted metabolomics studies were performed using liquid chromatography-mass spectrometry (LC-MS) to compare the metabolic characteristics of the feces of mice in each group and to find intestinal differential metabolites and potential differential metabolic pathways. The results showed that compared with the normal group, 5-hydroxy-L-tryptophan, histidine, L-acetylcarnitine, 16-hydroxy hexadecanoic acid, thromboxane B2, etc. were significantly up-regulated, L-urobilin and prostaglandin D3 were down-regulated in the feces of the model group, and were reversed after treatment with the rhubarb-peach kernel. The results of metabolic pathway enrichment analysis showed that tryptophan metabolism and histidine metabolism were the main intervention pathways of the rhubarb-peach kernel on AM intestinal metabolism. This study found that the underlying mechanism of the rhubarb-peach kernel in the treatment of AM is related to the intervention of intestinal metabolism of tryptophan, histidine, bile acid, choline and arachidonic acid, and the regulation of pro-inflammatory microenvironment and fatty acid metabolic homeostasis. This study has been approved by the Experimental Animal Ethics Committee of China Three Gorges University (No. 20190801).

  • Ping ZHANG, Hui JI, Qing-hua HU
    Acta Pharmaceutica Sinica. 2022, 57(7): 1954-1961.

    With the acceleration of the aging process of our country's population, the impact of aging-related diseases - Alzheimer's disease (AD) on society and families has become increasingly prominent. AD is caused by multiple mechanisms, and the pathogenesis has not been fully elucidated. Most of the clinical treatments are single therapy, which mainly focuses on improving symptoms and are difficult to reverse the disease process. Therefore, the development of drugs that can both improve symptoms and reverse the disease process is extremely urgent in clinical. Increasing number of studies has shown that traditional Chinese medicine plays an important role in the prevention and treatment of AD. The natural products have many advantages, such as novel structures, multiple targets and diverse activities, which can be used as an important source of leading compounds for the treatment of AD. The review summarizes the main clinical treatment methods and the research progress of natural ingredients in traditional Chinese medicine, and provides a reference for the follow-up clinical treatment of AD combined with the advantages of traditional Chinese medicine treatment.

  • Meng-yao LEI, Pei-pei GAO, Jian-gang LONG
    Acta Pharmaceutica Sinica. 2022, 57(7): 1925-1936.

    Alzheimer's disease (AD) and other aging-related diseases have become an important public health issue in China. However, current clinical drugs have failed to reverse the pathological process of AD. The holistic approach of traditional Chinese medicine offers advantages in improving cognitive function in AD through multiple molecular pathways, and may have potential for preventing AD. This paper summarizes the effects of classical traditional Chinese medicine and its active components in the improvement of AD-related cognitive dysfunction and describes the functional targets and related molecular mechanisms. This may have significance for the prevention and treatment of AD through multi-target intervention.

  • Yu-xin LIU, Xue-mei QIN, Li GAO
    Acta Pharmaceutica Sinica. 2022, 57(7): 1946-1953.

    Cell senescence is characterized by permanent cell cycle arrest, accompanied by the changes in cell metabolism and epigenetic regulation. Alzheimer's disease (AD) is a common neurodegenerative disease, with the main symptoms of memory loss and cognitive impairment. A large number of studies have shown that the senescence of central nervous system cells such as astrocytes and microglia is closely related to the occurrence of AD. Inhibition of brain cell senescence is expected to provide new ideas and therapeutic strategies for the prevention and treatment of AD. This paper reviews the potential roles and mechanisms of senescence of brain cells in AD, and interaction effects among brain cells. This review will provide a new direction for the study of pathological mechanism of AD and the development of anti-AD drugs.

  • Zeng-ping KANG, Hai-mei ZHAO, Meng-xue WANG, Jia-qi HUANG, You-bao ZHONG, Duan-yong LIU
    Acta Pharmaceutica Sinica. 2022, 57(7): 2068-2076.

    This study evaluated the regulatory effect of curcumin on memory follicular T cells (mTf) in obese mice with ulcerative colitis on the basis of determining its effective treatment of ulcerative colitis in obese mice. Forty male leptin mutant (ob/ob) mice were randomly divided into control group, control + curcumin group, dextran sodium sulfate (DSS) group and DSS + curcumin group, with 10 mice in each group. Mice in the DSS group and the DSS + curcumin group were induced by DSS to establish chronic ulcerative colitis model, and mice in the control + curcumin group and the DSS + curcumin group were given curcumin (200 mg·kg-1·d-1) by intragastric administration. Mice were sacrificed under anesthesia, and colon mass index, colon length and other conditions were observed in each group. Pathological injury of colonic was performed after HE staining. The levels of memory follicular helper T cells (mTfh) and memory follicular regulatory T cells (mTfr) in spleen of mice were detected by flow cytometry. The expression levels of interleukin-10 (IL-10) and interleukin-17A (IL-17A) in colon tissue were detected by ELISA. The results showed that curcumin significantly increased the body weight and colon length of obese mice with colitis, and decreased the colon weight, colon mass index and pathological score (P < 0.05). Curcumin significantly reduced the levels of central memory follicular T cells (cmTf), mTfh1, mTfh17 cells and the content of pro-inflammatory cytokine IL-17A (P < 0.01). The levels of effector memory follicular T cells (emTf) and mTfr and the content of anti-inflammatory cytokine IL-10 were increased (P < 0.05, P < 0.01). Therefore, curcumin may treat colitis in obese mice by regulating the balance of mTf cell subsets.

  • Chang-yuan ZHENG, Xu SU, Yu-ping LIU, Tao LIU, Ya-nan WANG, Dan-dan SU, Yu ZHANG, Na QIN
    Acta Pharmaceutica Sinica. 2022, 57(7): 2224-2233.

    Cirsium souliei (Asteraceae) is a perennial medicinal herb of Cirsium with important medicinal and ecological values. Here, we sequenced the complete chloroplast (cp) genome of C. souliei based on high-throughput sequencing technology, then assembled and annotated it, and analysed the structure and characteristics of the cp genome. The result indicated that the cp genome of C. souliei was a typical quadripartite circular structure of 152 470 bp in length, and GC content was 37.7%. The cp genome of C. souliei encoded 134 genes, including 89 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Meanwhile, we detected 188 simple sequence repeats (SSR) loci in the cp genome, which were mainly composed of mononucleotide repeats. Codon bias analysis showed that leucine (Leu) was the highest amino acids with frequency (10.51%), and there were 30 codons with the value of relative synonymous codon usage (RSCU) above one, of which mostly ended with A/U. Additionally, the result from phylogenetic analysis based on 46 cp genomes of Carduoideae showed that C. souliei and C. vulgare were sister species, and had the closest relationship with 100% bootstrap within Cirsium. This study provides theoretical basis for future studying genetic diversity, population genetic structure, systematics and evolution, and speciation mechanism.

  • Qing-yu LI, Jing-jing GAO, Yan-jin FU, Meng-sha LONG, Yi-yao ZHANG, Zu-yu MENG, Shao-zi LIN, Jia-jia QIN
    Acta Pharmaceutica Sinica. 2022, 57(7): 2108-2114.

    The purpose of this study was to investigate how Zuogui pills from the Kidney-tonifying and Nourishing Yin formula, in combination with the gonadotrophin-releasing hormone antagonist cetrorelix, affected the ovarian local oxidative stress response in decreasing ovarian reserve (DOR) mice. All animal experiments were carried out in accordance with the guidelines and standards established by Jinan University's Experimental Animal Management Committee. Cyclophosphamide (CTX)-treated DOR mice were given Zuogui pills, cetrorelix, or a combination of the two drugs intragastrically. After treatment, there were changes in the estrous cycle, serum sex hormone levels, oxidative stress-related indexes, growth biochemical factor levels, and SIRT1/P53/P21 expression. In comparison to the model group, the Zuogui pills and the cetrorelix+Zuogui pills group had significantly prolonged estrous periods and shortened interestrous periods, and the cetrorelix+Zuogui pills group had a significantly shortened cycle length. Follicle-stimulating hormone (FSH) decreased and estradiol (E2) increased in all treatment groups compared to the model group, oxidative stress indexes nitric oxide synthase (NOS), nitric oxide (NO), and reactive oxygen species (ROS) decreased, growth biochemical factors brain derived neurotrophic factor (BDNF) and growth differentiation factor 9 (GDF-9) concentrations increased significantly, and leukemia inhibitory factor (LIF) showed no significant change. SIRT1/P53/P21 immunohistochemical results revealed that, when compared to the model group, the expression of SIRT1 increased while the expression of P53 and P21 proteins decreased in all treatment groups, with the cetrorelix+Zuogui pills group having the largest decrease, with significant differences in all indicators. We conclude that cetrorelix combined with Zuogui pills for kidney nourishing and Yin recipe improved the oxidative stress response in the follicle by regulating the SIRT1/P53/P21 pathway, reducing peroxide product production, protecting ovarian function, and regulating ovarian hormone secretion, and its efficacy is superior to that of cetrorelix or Zuogui pills alone.

  • Yong ZHANG, Akber Aisa HAJI, Wei-liang ZHU
    Acta Pharmaceutica Sinica. 2022, 57(7): 2139-2145.

    Ten compounds were isolated from the water extract of Eriocaulon buergerianum by HP20, ODS, Sephadex LH-20 and MCI Gel CHP-20 column chromatographic methods. Their structures were identified by spectroscopic and chemical approaches as 6-methoxyquercetin-3-O-(2'''-vanilloyl)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (1), syringaresinol-4'-O-β-D-glucopyranoside (2), rutin (3), 1-O-feruloylglycerol (4), 1, 2-benzenediol (5), vomifoliol (6), β-D-(6-O-trans-feruloyl) fructofuranosyl-α-D-O-glucopyranosied (7), dihydroferulic acid (8), guanosine (9) and quercetin-3-O-β-gentiobioside (10). The compound 1 is a new compound, the compounds 2 and 4-10 were obtained from Eriocaulon genus for the first time, and the compound 3 was isolated from this plant for the first time. Molecular docking study showed that 1 is a potential inhibitor of TNF-α. The compound 1 was evaluated for their anti-inflammatory activities in vitro, and 1 showed significant inhibitory activity against TNF-α production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells at the concentrations of 1, 10 and 100 μmol·L-1.