南京中医药大学学报

Quality Control of the Production Process Based on Substance-Related-Effects for Chinese Patent Medicine

XIAO Wei, ZHANG Xin-zhuang, CAO Liang, WANG Zhen-zhong

2022, 38(9): 743-747. doi: 10.14148/j.issn.1672-0482.2022.0743

[Abstract](356) [FullText HTML] (51) [PDF 4405KB](32)

Abstract:
Chinese patent medicine is a modern dosage form of traditional Chinese herbal formula, which confrom to the inheritance and innovation of traditional Chinese medicine (TCM). How to identify substance-related-effects and control the quality of the products is the most critical issue in the manufacturing process of Chinese patent medicine including exctraction, purification, concntration, drying. According to the R&D pratice for many years, "substance-related-effects" are put forward and regarded as indicator to build the Quality Control of the production process, hoping to obtain perfornance products with reliable effects and consisten quality.

Study on the Material Base of Tripterygium Glycosides Tablet against Human Acute Monocytic Leukemia

FANG Bing-qian, WANG Ya-nan, LIU Yan, WANG Xia-chang, KANG Di, HU Li-hong

2022, 38(9): 748-760. doi: 10.14148/j.issn.1672-0482.2022.0748

[Abstract](341) [FullText HTML] (49) [PDF 2719KB](28)

Abstract:
OBJECTIVE To discovery sensitive cell lines of tripterygium glycosides tablet against different subtypes of hematological tumors, and to find out the material base for the effect on proliferative inhibition against sensitive cell lines. METHODS The CCK-8 assay was used to assess the effect of tripterygium glycosides tablet and its extract on cell proliferation in vitro; Then, the in vivo subcutaneous xenograft models by injecting sensitive cells were constructed to test the inhibitory activity of tripterygium glycosides tablet; Furthermore, the extract of tripterygium glycosides was systemically chemical investigated by chromatographic separation techniques, mass spectrometry, and nuclear magnetic resonance, and anti-human acute monocytic leukemia (AMOL) activity was tested for each compound; In the end, preparative HPLC was used for the specific removal of triptolide (TP) from the extract of tripterygium glycosides. The anti-AMOL activity was measured and analyzed after removing TP from the formulations of T. wilfordii. RESULTS The results of cell experiments indicated that tripterygium glycosides exhibited potent anti-AMOL activity; Next, in vivo tumor xenograft models showed tripterygium glycosides significantly inhibited the growth of subcutaneous tumor xenografts of AMOL cells; Furthermore, chemical constituents of tripterygium glycosides extract were isolated systemically, the activity were evaluated at the cellular level. It was found that TP showed the strongest anti-AMOL activity. Finally, it was found that the IC₅₀ values of the tripterygium glycosides tablet and its extract against AMOL cells increased 8 and 13 fold, respectively, after removing TP. CONCLUSION Tripterygium glycosides tablet shows significant inhibitory activity against acute monocytic leukemia cells, and its diterpenoid, triptolide, is the most active ingredient.

Expanded Applications and Applicable Population Characteristics of Huangqin Decoction

HUANG Huang

2022, 38(9): 761-764. doi: 10.14148/j.issn.1672-0482.2022.0761

[Abstract](181) [FullText HTML] (35) [PDF 1727KB](27)

Abstract:
Huangqin decoction is a classic formula for treating diarrhea in febrile diseases, and later became the basic formula for treating damp-heat diarrhea in the successive generations. This study introduces the expanded applications and the characteristics of its applicable population. In addition to the original text of Treatise on Cold Damage, Huangqin decoction can also be used in modern clinical practice for febrile diseases, gastrointestinal diseases, obstetrical and gynecological diseases, as well as autoimmune diseases. From the viewpoint of the applicable population, Huangqin decoction is mostly applied for a yin-deficiency or damp-heat constitution caused by internal heat or latent heat, which is more common in female population. Besides, it has specificity to apply the formula based on some typical symptoms or syndromes, such as mucosal hyperemia, dysphoria with smothery sensation, and anorectal discomfort. Thus, the mentioned syndromes are also called the indications of Huangqin decoction. The clinical thinking of identifying the indications of Huangqin decoction is inseparable from its applicable disease and applicable population.

Exploring the Connotation of Anti-tumor Metastasis by Supplementing Qi, Invigorating Blood from the Syndrome Differentiation Between the Static and Dynamic Process

YU Qian-hui, LIU Fu-yan, YIN Gang, LIU Min, ZHAO Fan, LIANG Zhong-qin, SUN Ruo-lan, LIANG Yan, GAO Jin, YIN Ying, XU Meng, TANG De-cai

2022, 38(9): 765-769. doi: 10.14148/j.issn.1672-0482.2022.0765

[Abstract](170) [FullText HTML] (27) [PDF 2127KB](21)

Abstract:
Tumor treatment in Chinese medicine has been used to invigorate blood, but this is a controversial issue in academic circles. The reasons for this are based on the premise that tumor metastasis is a completely "dynamic" process, and that its applying can control the spread and metastasis of tumor. Inspired by the theory of "spreading and lingering of cancer toxin" in the "Huangdi's Cannon of Medicine", according to the literature and the previous research results, tumor metastasis is a combination of dynamic and static process. Especially the "static" process of cancer embolus adhering to the inner wall of blood vessels is more critical. The formula with the function of supplementing qi and invigorating blood can reduce blood stasis, restrain tumor metastasis, and strengthen the adhesion between homogeneous tumor cells to a certain extent. Thus, that treatment has a biphasic effect on anti-tumor metastasis. In this regard, the use of the formula with the function of supplementing qi and invigorating blood for anti-tumor treatment should become the conventional therapy.

Expression Analysis of Two Chemical-Types of Artemisia Annua L. Terpenoids and Their Related Genes

WANG Ting-ting, DAI Shi-lin, LIU Chan-chan, JIANG Zheng, WU Qi-nan

2022, 38(9): 770-779. doi: 10.14148/j.issn.1672-0482.2022.0770

[Abstract](198) [FullText HTML] (35) [PDF 4485KB](8)

Abstract:
OBJECTIVE To investigate the differential metabolites of two chemical-types of Artemisia annua and their possible causes by analyzing the data of terpenoid metabolites and their transcriptome of two chemical-types of Artemisia annua. METHODS The seeds of Artemisia annua were collected from Xuyi County, Jiangsu Province, and Zhongmou County, Henan Province, in China, and grown under the same conditions. The volatile components of Artemisia annua were analyzed by headspace-gas chromatography-triple quadrupole mass spectrometry (HS-GC-QQQ-MS/MS), non-targeted analysis of the differential metabolites of 2 chemical-types of Artemisia annua were performed by ultra-fast liquid chromatography-triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS), and the expression of the biosynthetic genes of the volatile components was analyzed by transcriptome sequencing. RESULTS Based on the typing of volatile components, Artemisia annua from Xuyi County, Jiangsu Province was classified as artemisia ketone type, and Artemisia annua from Zhongmou County, Henan Province was classified as camphor type. The differential metabolites detected by UFLC-Triple TOF-MS/MS were significantly up-regulated in sesquiterpene, triterpene, and diterpene biosynthesis pathways by Kyoto encyclopedia of genes and genomes (KEGG) database analysis for artemisia ketone type and camphor types of Artemisia annua, respectively. The 2-methyl-D-erythritol-4-phosphate (MEP) pathway leading to terpene skeleton biosynthesis and the mevalonate (MVA) pathway annotated 23 candidate genes for 11 key enzymes that were significantly differential in the transcriptome data. In the monoterpene synthesis pathway, 10 candidate genes were detected for 1, 8-cineole synthase (TPS-Cin). In addition, two borneol dehydrogenase candidates were found to be highly expressed in camphor-type Artemisia annua, and three Artemisia annua alcohol dehydrogenase (ADH2) candidates were highly expressed in artemisia ketone-type Artemisia annua. CONCLUSION This study provides scientific data to reveal the molecular mechanism of Artemisia annua chemical-types formation.

Review on the Application of Common Formulations and Generic Techniques of Children's Chinese Medicine Preparations

LI Neng-jin, FENG Ya-ru, WANG Ruo-ning, ZHAO Xiao-li, XIE Hui, ZHANG Wen, DI Liu-qing

2022, 38(9): 780-789. doi: 10.14148/j.issn.1672-0482.2022.0780

[Abstract](250) [FullText HTML] (49) [PDF 1764KB](26)

Abstract:
Currently, adultification phenomenon in formulation selection, excipient optimization, process design, package equipment of children's Chinese medicine preparations are common, resulting in inaccurate dosage, poor medication compliance, difficulties in ensurance of drug's effectiveness and safety, as well as frequent adverse drug reactions. Therefore, it is urgent to investigate the preparations that conform to the characteristics of children's medication and break through the key technologies of children's preparations. This article analyzes the oral liquid, syrup, granule and other dosage forms, meanwhile discusses their application in Chinese medicine preparations for children. At the same time, on the issues of low solubility, poor taste and inaccurate dosage in children's Chinese medicine preparations, the characteristics and utilization of generic technologies such as solubility enhancement, taste masking and quantitative administration are discussed. The review aims to lay a foundation and provide a basis for the research and development of children's Chinese medicine preparations.

Discussion on Research Ideas of Intervention of β-Amyloid Metabolism with Linggui Zhugan Decoction to Regulate Spleen's Governing Transportation and Transformation

WANG Li-lan, ZHOU Chun-xiang

2022, 38(9): 790-796. doi: 10.14148/j.issn.1672-0482.2022.0790

[Abstract](292) [FullText HTML] (46) [PDF 2912KB](18)

Abstract:
The clearance of excessive β-amyloid (Aβ) in the brain is mainly degraded and cleared by autophagy lysosomal system, protease secreted by astrocytes and phagocytosis of microglia. It can also be transported and discharged through blood-brain barrier or brain lymphatic drainage system. The function of spleen in regulating transportation and transformation Aβ metabolism plays an important role. Many experimental evidence shows that Linggui Zhugan decoction, the representative of Wenpi Huayin method, may affect Aβ structures and functions of metabolic related pathways. This paper discusses the scientific connotation transportation and transformation for clear Aβ based on the mechanism of Aβ metabolic pathway and the analysis of the pharmacological effect of Linggui Zhugan decoction, in order to explore the idea of traditional Chinese medicine treatment of Alzheimer's disease.

Syndrome Differentiation and Treatment of Constraint Syndrome Based on the Theory of Resolving the Fire Constraint

QI Ming-ming, GUO Ren-qing, MA Jian, TAO Wei-wei

2022, 38(9): 797-802. doi: 10.14148/j.issn.1672-0482.2022.0797

[Abstract](343) [FullText HTML] (74) [PDF 1063KB](48)

Abstract:
Depression is a mental illness that seriously affects public health, but its etiology and pathogenesis have not been fully elucidated. According to the clinical manifestations, Chinese medicine classifies depression as a constraint syndrome. By sorting out the meaning of constraint, it is found that constraint involves both the etiology and pathogenesis, as well as the disease per se. The pathogenesis and clinical manifestations of depression coincide with those of the constraint syndrome in Chinese medicine. Thus, the clinical diagnosis and treatment can be made by referring to the "constraint syndrome" in Chinese medicine. Considering "fire constraint" is the key pathogenesis of depression changing from mild to severe, the clinical treatment of "fire constraint" should be based on the principle of differentiating the deficiency or excess syndrome. For example, the treatment on the excess syndrome of the fire constraint should be clearing and purifying, while the treatment of the deficiency-excess complex should be unblocking and reinforcing.

Clinical Study on the Effect of Jingling Granules on Vascular Elasticity in Patients with Atherosclerosis

GONG Fanying, ZOU Fei, ZHU Yan, ZHOU Mei-hui, DU Yu-ying, WANG Shun, ZHANG Chun-qin, YU Qiu-yu, LIU Fu-ming

2022, 38(9): 803-809. doi: 10.14148/j.issn.1672-0482.2022.0803

[Abstract](71) [FullText HTML] (11) [PDF 1101KB](20)

Abstract:
OBJECTIVE To observe the effects of Jingling granules on the traditional Chinese medicine (TCM) syndrome score, arterial elasticity and morphological function, blood lipids, blood rheology, as well as serum inflammatory factors in patients with atherosclerosis of qi-yin deficiency and phlegm-blood stasis. METHODS A total of 100 patients with atherosclerosis who met the inclusion criteria were randomly divided into control group and experimental group, 50 patients in each group. The control group was treated with atorvastatin, while the experimental group was administered with Jingling granules based on the treatment of the control group. The changes in the two groups were compared in terms of the TCM syndrome score, carotid intima-media thickness (IMT), ultrafast pulse wave velocity (UFPWV) indexes [pulse wave velocity-beginning of systole (PWV-BS), pulse wave velocity-end of systole (PWV-BS), pulse wave velocity-end of systole (PWV-ES)], blood lipids, blood rheological indexes (whole blood high shear viscosity, whole blood medium shear viscosity, whole blood low shear viscosity, plasma viscosity), serum inflammatory factors C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), as well as the liver and kidney function. RESULTS After treatment, the TCM syndrome scores of the two groups were significantly reduced (P < 0. 01), but the result of the experiment group was better than that of the control group (P < 0.01). The bilateral carotid PWV-BS and PWV-ES of the experiment group were reduced (P < 0.01), and the bilateral carotid PWV-ES and left carotid PWV-BS of the control group were reduced (P < 0.05), but the change of the right carotid PWV-ES of the experiment group was better than that of the control group (P < 0.05). The levels of TC, TG and LDL-C showed better results in both groups (P < 0.01), while the change of TC level was better in the experiment group than in the control group (P < 0.01). Besides, the levels of whole blood medium shear viscosity and whole blood low shear viscosity, as well as plasma viscosity were reduced in both groups (P < 0.05), but the change of whole blood low shear viscosity showed better result in the experiment group than in the control group (P < 0.05). In addition, the levels of serum CRP, IL-6 and IL-8 were reduced in the experiment group (P < 0.05), and the levels of IL-6 and IL-8 were reduced in the control group (P < 0.05). However, the changes of CRP levels in the experiment group were better than those in the control group (P < 0.05). No significant adverse reactions were observed in both groups during the treatment. CONCLUSIONS Jingling granules, combined with atorvastatin, can achieve the better clinical efficacy in treating patients with atherosclerosis of qi-yin deficiency and phlegm-blood stasis, in terms of the TCM syndrome scores, vascular elasticity, TC, TG, LDL-C levels, inflammatory factors CRP, IL-6, IL-8 levels, the levels of whole blood medium shear viscosity, whole blood low shear viscosity, and plasma viscosity.

Yangyin Qingre Formula Regulates Treg/Th17 Balance by Down-Regulating JAK/STAT Signaling Pathway

ZHANG Lin-hui, MA Yuan-jing, MIU Rong, WANG Wei, WENG Wen-xin, YUAN Dong-ping, LONG Jun, SUN Yunxia

2022, 38(9): 810-818. doi: 10.14148/j.issn.1672-0482.2022.0810

[Abstract](136) [FullText HTML] (16) [PDF 3784KB](22)

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OBJECTIVE To investigate the effect and mechanism of Yangyin Qingre formula (YHF) on Treg/Th17 imbalance induced by lipopolysaccharide (LPS) in mice. METHODS CD4⁺ T cells from mouse spleen were extracted by magnetic bead sorting method and CD4⁺ T cells differentiation was stimulated by LPS followed by intervention with 1, 2, 4 mg · mL^-1 YHF. Cells proliferation was detected by MTT method. The ratio of Treg/Th17 of CD4⁺ T cells subsets was detected by flow cytometry. The expression of cytokines (IL-10, TGF-β, IL-6, IL-12p70) in cells supernatant was measured by ELISA. The expression of Foxp3, RORγt, and the signalling molecules JAK/STAT in the cells were detected by Western blot. RESULTS HPLC identified eight active ingredients of YHF, namely hydroxy saffron yellow pigment A, polydatin, rutin, 2, 3, 5, 4'-tetrahydroxystilbene glucoside, resveratrol, quercetin, emodin and curcumin. YHF dose-dependently inhibited the proliferation of LPS-stimulated mouse CD4⁺ T cells (P < 0.05), increased the proportion of Treg (P < 0.05) and decreased the proportion of Th17 (P < 0.01), promoted the secretion of Treg-related anti-inflammatory factors IL-10 and TGF-β in culture supernatant and inhibited the secretion of Th17-related pro-inflammatory factors IL-6 and IL-12p70 secretion. 1, 2, 4 mg · mL^-1 YHF increased the expression of Foxp3 protein (P < 0.05) and decreased the expression of RORγt protein (P < 0.01). 1, 2, 4 mg · mL^-1 YHF decreased the expression of JAK2, STAT3 and their phosphorylated proteins (P < 0.05). The combination of 4 mg · mL^-1 YHF with the JAK2-specific inhibitor AG490 increased culture supernatant IL-10 and TGF-β levels (P < 0.05), decreased IL-6 and IL-12p70 levels (P < 0.05) and more significantly decreased p-JAK2, p-STAT3 and RORγt protein expression (P < 0.01, P < 0.001) and increased Foxp3 protein expression (P < 0.01). CONCLUSION YHF can effectively inhibit the proliferation of inflammatory LPS-induced CD4⁺ T cells by suppressing the expression of JAK2 and STAT3 signaling molecules, increase the expression of Foxp3 and the number of Treg, decrease the expression of RORγt and the number of Th17, increase the secretion of anti-inflammatory cytokines IL-10 and TGF-β and inhibit the secretion of pro-inflammatory cytokines IL-6 and IL-12p70.

Qianggu Decoction Promotes Angiogenesis through Wnt3a/β-catenin/VEGF Pathway to Improve Osteoporosis in Perimenopausal Rats

WANG Yu-chen, RUI Li-ning, JIA Chuan, YU Wei-zhong

2022, 38(9): 819-826. doi: 10.14148/j.issn.1672-0482.2022.0819

[Abstract](106) [FullText HTML] (25) [PDF 4529KB](17)

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OBJECTIVE To investigate the efficacy and possible mechanism of action of the Chinese medicinal preparation Qianggu decoction on perimenopausal osteoporotic SD rats. METHOD HPLC was used to establish the standard fingerprint profile of Qianggu decoction. Fifty SD rats were randomly divided into sham-operated group, model group, estradiol valerate group, and high (12 g · kg^-1) and low (6 g · kg^-1) dose groups of Qianggu decoction, with 10 rats in each group. The perimenopausal osteoporosis rat model was prepared by bilateral ovariectomy method, and saline, estradiol or high and low doses of Qianggu decoction were administered by gavage for 30 days. The weight and uterine weight of the rats were recorded, and the bone mechanics related indexes were measured, and the number of osteoblasts and the area of bone trabeculae in the femur were observed by HE staining. Wnt3a, β-catenin, VEGF and OPG gene expression levels were detected by PCR; VEGFR-2 and CD31 were detected by immunofluorescence, and angiogenesis was evaluated. The protein expression of Wnt3a, p-GSK3β, VEGF, β-catenin, Lamin were detected by Western blot. RESULTS The fingerprint similarity of the 10 batches of Qianggu decoction was greater than 0.9, indicating that the quality of the 10 batches of samples was stable. Compared with the model group, estradiol valerate-treated group and high and low dose Qianggu decoction-treated groups could significantly improve the uterine index, bone density and bone mechanical properties of rats(P < 0.05, P < 0.01), significantly improve bone microstructure, and increase the levels of Wnt3a, β-catenin, VEGF, OPG mRNA in femoral tissue(P < 0.05, P < 0.01), as well as VEGF, CD31, Wnt3a, p-GSK3β, β-catenin, Lamin protein expressions(P < 0.05, P < 0.01). CONCLUSION Qianggu decoction may regulate VEGF expression and promote angiogenesis through Wnt3a/β-catenin signaling pathway, thus increasing bone density and improving bone tissue morphology in rats, and then exerted anti-osteoporosis effects.

Professor Xu Zhi-yin's Experience in Treating Breast Cancer-Related Lymphedema by Tonifying Qi and Invigorating Blood Combined with Unblocking the Collaterals and Promoting Urination

WANG Cong, YAO Chang, SONG Bo-yang

2022, 38(9): 827-830. doi: 10.14148/j.issn.1672-0482.2022.0827

[Abstract](146) [FullText HTML] (40) [PDF 1014KB](16)

Abstract:
Professor Xu Zhi-yin's clinical experience in diagnosing and treating breast cancer-related lymphedema concluded that postoperative breast cancer lymphedema is deficiency in root and excess in manifestation. Considering it is deficiency in the root, its pathogenesis is closely related to the liver, lung and spleen, and the main pathogenic factors are blood stasis, qi stagnation, and water-dampness. Based on the treatment principle of reinforcing healthy qi and expelling the pathogenic factors, the specific treatments are established, such as benefiting qi, nourishing blood, unblocking the collaterals, as well as promoting urination. Clinically, the Honghuang decoction is the basic formula. In addition, physicians need to distinguish the manifestations and root causes, to keep a sense of proportion, to focus on the individual treatment, to modify the decoction according to the syndrome changes, and to choose medicinals on the grounds of different constitutions. In conclusion, physicians should follow the idea of "treating disease before its arising", which is strengthen the healthy qi and eliminate potential harmful factors to prevent the occurrence or development of a disease, to achieve the best therapeutic effect.

Textual Research on the Variety of Processing Medicinals and Prescription Dosage of the Classic Formula: Gualou Xiebai Banxia Decoction

WANG Yuan-biao, SHEN Jie

2022, 38(9): 831-838. doi: 10.14148/j.issn.1672-0482.2022.0831

[Abstract](391) [FullText HTML] (70) [PDF 1127KB](15)

Abstract:
By collecting data from ancient traditional Chinese medical (TCM) texts, combining the clinical experience of TCM practitioners and modern pharmacological research results of Chinese medicine, we systematically analyzed the variety of processing medicinals and prescription dosage of Gualou Xiebai Banxia decoction, to provide a textual reference for the development and clinical application of the classic formula. It was proved that the "white wine" in Gualou Xiebai Banxia decoction was mild rice wine (alcohol content: 10%-20%), and the rest of the variety of processing medicinals should be raw Gualou, raw Xiebai and ginger processed Banxia. In addition, it was found that the dosage of Banxia should be half-liter (reference to the Essentials from the Golden Cabinet of Wu Qian's version). The modern TCM clinical reference dosage of the classic formula is listed as follows: Gualou 15 g, Xiebai 12 g, Banxia 16 g, and white wine 500 mL.

2022 Vol. 38, No. 9

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