南京中医药大学学报

Exploration on the "Eight Methods of Discriminating Drugs" in Transforming the Significance of Medicinal Substances

LUO Xi-lei, WU Qin-yao, PENG Shun-lin

2023, 39(5): 401-406. doi: 10.14148/j.issn.1672-0482.2023.0401

[Abstract](365) [FullText HTML] (40) [PDF 983KB](45)

Abstract:
This paper introduces the current research status and existing problems of the theory of traditional Chinese drug properties, as well as the specific meanings and theoretical sources of the "eight methods of discriminating drugs". The "eight methods of discriminating drugs" theory analyzes drugs through the eight dimensions of body, color, qi, taste, form, nature, energy, and power, attempting to find the fundamental composition laws and deconstruction methods of traditional Chinese drug properties. It is believed that the "eight methods of discriminating drugs" theory has established a comprehensive system for evaluating the properties of traditional Chinese drugs at the level of traditional Chinese medicine theory, which can be used as a reference for modern researchers of traditional Chinese drug property theory in explaining the "nature-effect-use" relationship of traditional Chinese drug and establishing a diverse theoretical research system for drug properties.

Analysis of the Syndrome of "Two Infected with Cold Pathogen" in The Yellow Emperor's Inner Classic and "Two Infected with Pathogen" in Treatise on Cold Damage

MA Jun-jie

2023, 39(5): 407-410. doi: 10.14148/j.issn.1672-0482.2023.0407

[Abstract](215) [FullText HTML] (69) [PDF 943KB](43)

Abstract:
Summarize the historical evolution of the connotation of "two infected with cold pathogen" in The Yellow Emperor's Inner Classic, and propose that the "two infected with cold pathogen" in The Yellow Emperor's Inner Classic is the condition where Taiyang and Shaoyin meridians simultaneously infect cold pathogen when Shaoyin is deficient. This belongs to a critical syndrome, and is significantly different from the "two infected with pathogen" syndromes of Taiyang and Shaoyin meridians proposed in Treatise on Cold Damage. The "two infected with pathogen" in Treatise on Cold Damage has narrow meaning and broad meaning. The narrow meaning specifically refers to the infection of pathogen in both the external and internal meridians; while the broad meaning proposes that despite how the disease occurs and spreads, as long as the two meridians are infected with pathogen, it belongs to the category of "two infected with pathogen". The broad meaning not only involves complex diseases of both the external and internal meridians, but also includes related contents of complex and combination diseases of other two meridians, and even the same meridian-mediated meridian-organ diseases. Referring to the treatment of "two infected with pathogen" in Treatise on Cold Damage, it is proposed that the "two infected with cold pathogen" in The Yellow Emperor's Inner Classic can be first treated with Sini decoction or Tongmai Sini decoction for the interior, and then decide whether to use Guizhi decoction, etc, to relieve external symptoms based on the condition.

UPLC-Q-TOF-MS/MS Metabolomics Analysis of the Effect of Acupuncture on Changes in Plasma Metabolites in Patients with Depression

ZENG Rui, KANG Dong-ni, WANG Xing, WANG Hong, CHEN Bin, WANG Jing, HUANG Yi-ping

2023, 39(5): 411-419. doi: 10.14148/j.issn.1672-0482.2023.0411

[Abstract](120) [FullText HTML] (38) [PDF 3184KB](33)

Abstract:
OBJECTIVE Using UPLC-Q-TOF-MS/MS to study the potential biomarkers of acupuncture in the treatment of depression, and to explore the potential metabolic regulatory mechanism of acupuncture treatment for depression. METHODS 25 depression patients from Nanjing brain hospital from October 2017 to June 2018 were selected and randomly divided into 13 cases in acupuncture drug group and 12 cases in drug group(with 4 cases fell off). The drug group received oral treatment with SSRIs, while the acupuncture drug group received ear endothelial puncture treatment in addition to the treatment of drug group. Plasma samples were collected from the two groups of patients before and after treatment, and UPLC-Q-TOF-MS/MS was used to detect plasma metabolites before and after treatment. The differences in metabolites between the two groups were compared before and after treatment. RESULTS 16 potential biomarkers were screened out in the acupuncture drug group. It is speculated that the acupuncture drug group can improve the abnormal metabolism of patients with depression by regulating phenylalanine metabolism, histidine metabolism, synthesis and degradation of ketone bodies, and lysine degradation. 9 potential biomarkers were screened out in the drug group. It is speculated that the acupuncture drug group improves abnormal metabolism in patients with depression by regulating the four metabolic pathways: phenylalanine metabolism, histidine metabolism, ketone synthesis and degradation, and lysine degradation. CONCLUSION The regulation of metabolites in patients with depression may be the internal mechanism by which acupuncture exerts its antidepressant effect.

Using Lipidomics Technology to Investigate the Regulatory Impact of Jianpi Lishi Formula on Lipid Metabolism in NAFLD Mice

JIN Tian-zi, LUO Zi-chen, XU Wei-chen, CHONG Ying, SHI Chen, SHAN Jin-jun

2023, 39(5): 420-432. doi: 10.14148/j.issn.1672-0482.2023.0420

[Abstract](220) [FullText HTML] (21) [PDF 2020KB](34)

Abstract:
OBJECTIVE To explore the regulatory effect of Jianpi Lishi Formula on liver lipid metabolism in NAFLD mice based on LC-MS lipidomics. METHODS C57BL/6J mice were randomly divided into three groups: blank group, model group, and Jianpi Lishi Formula group, with 6 mice in each group. NAFLD models were induced by feeding them 60% high-fat feed for 12 weeks, during which medication intervention was also performed. The pharmacodynamic evaluation was conducted through biochemical indicator detection and pathological sections, while LC-MS lipidomics was used to detect lipid changes in mouse liver tissue. RESULTS Jianpi Lishi Formula improved the increase in body mass induced by HFD. HE and oil red staining showed that it had a liver protective effect and could restore glucose metabolism levels. Also, Jianpi Lishi Formula decreased the mRNA levels of Fasn, CD36, SCD1, and Srebp1c in the liver (P < 0.05, P < 0. 01, P < 0. 001). Lipidomics research found that Jianpi Lishi Formula has a regulatory effect on liver lipid composition. CONCLUSION Jianpi Lishi Formula has the effects of reducing body mass, regulating blood sugar, and protecting the liver. Lipidomics study indicates that the relief of NAFLD induced by Jianpi Lishi Formula may be related to the regulation of liver lipid composition.

Determination of Tissue Distribution of Phellodendrine and Its Glucuronide in Rat by LC-MS/MS

WANG Hao, LIU Xiao-li, LIN Ai-hua, LIU Yi-ming

2023, 39(5): 433-441. doi: 10.14148/j.issn.1672-0482.2023.0433

[Abstract](87) [FullText HTML] (14) [PDF 2410KB](10)

Abstract:
OBJECTIVE To establish an LC-MS/MS method to simultaneously determinate phellodendrine (PHE) and its glucuronide-Phellodendrine-11-O-β-D-glucuronide(M1), Phellodendrine-2, 11-di-O-β-D-glucuronide(M2) in rat tissue, and investigate the distribution characteristics of PHE, M1 and M2 in various tissue. METHODS Normal SD rats were administrated with phellodenine at the dosage of 40 mg·kg^-1, and the heart, liver, spleen, lung, kidney, brain, muscle, pancreas and small intestine were clipped at 0.117, 0.17, 0.5, 1, 2, 3, 4 hour after administration.Tissue homogenate samples were pretreated via protein precipitation with methanol, aconitine was used as the internal standard (IS). Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C₁₈ column (150 mm×2.1 mm, 3.5 μm) using a gradient elution of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL·min^-1.The column temperature was maintained at 35 ℃. Quantification was performed on an API 4000⁺ triple-quadrupole mass spectrometer equipped with a turbo electrospray ionization (ESI) source in positive ion multiple reaction monitoring (MRM) mode. RESULTS Excellent linearity of PHE, M1 and M2 was observed in all analytes within the ranges of 1-800, 1-1 000, 5-1 000 ng·mL^-1. Intra- and inter-day relative standard deviations (RSDs) were less than 11.07%, and accuracy were (91.58±1.84)%~(110.67±5.20)%. PHE, M1 and M2 were distributed in all the tissues. PHE tissue exposure was in the order of small intestine>liver>kidney>lung>pancreas>muscle>spleen>heart>brain. The manifestations of M1 and M2 were small intestine>kidney>liver>heart>lung>pancreas>muscle>spleen>brain. CONCLUSION The established method has strong specificity, high accuracy and good stability, and is suitable for the study of tissue distribution of PHE, M1 and M2. The results of tissue distribution showed that PHE, M1, M2 were widely distributed in rats, mainly in small intestine, kidney and liver.

Effects of Four Commonly Used Chinese Medicines with Clearing Heat and Drying Dampness on Intestinal Flora Mediated Bile Acids and Short Chain Fatty Acids Metabolism

LI Xin-ru, SHENG Xian-jie, YANG Yan, AN Zhen-tao, KANG An, LI Hui, GE Fei

2023, 39(5): 442-451. doi: 10.14148/j.issn.1672-0482.2023.0442

[Abstract](230) [FullText HTML] (37) [PDF 4307KB](27)

Abstract:
OBJECTIVE To explore the effects of four kinds of heat-clearing and dampness-drying herbs on intestinal flora, bile acids and short chain fatty acids (SCFAs) in normal mice at long-term clinical equivalent doses. METHODS Thirty Balb/c male mice were randomly divided into control group, Sophora flavescens Ait. (KS) group, Phellodendron chinense Schneid. (HB) group, Coptis chinensis Franch. (HL) group and Scutellaria baicalensis Georgi (HQ) group, with 6 mice in each group. Except for the control group, KS group, HB group, HL group and HQ group were orally administrated at a dosage of 2.34 g·kg^-1, 3.12 g·kg^-1, 1.3 g·kg^-1 and 2.6 g·kg^-1, respectively, for two weeks. The contents of short chain fatty acids and bile acids in feces were detected by liquid chromatography tandem mass spectrometry, and the structural changes of microflora in intestinal contents were detected by 16S rRNA high-throughput gene sequencing technology. RESULTS There was no significant effect of heat-clearing and dampness-drying Chinese medicine on the contents of six short-chain fatty acids in the feces of normal mice. Among the 23 common bile acids, when compared with the control group, the numbers of the significantly changed bile acids in HQ group, KS group, HL group and HB group were 4, 3, 2 and 1, respectively. From the perspective of changes in the abundance of intestinal flora, compared with the control group, except for the KS group, Firmicutes in the HL group, HQ group and HB group all showed a downward trend, and the Bacteroides showed an upward trend, among which the changes in the HL group were the most significant. CONCLUSION Sophora flavescens Ait., Phellodendron chinense Schneid., Coptis chinensis Franch. and Scutellaria baicalensis Georgi have little effect on SCFAs in normal mice, but can affect bile acid content by changing the structure of intestinal flora.

Study on HPLC-Q-TOF/MS Analysis and Fingerprint of Classic Prescription Wenjing Decoction Substance Benchmarks

TANG Zhi-feng, ZHANG Yun-yu, SHI De-zhi, GAO Wu-feng, GONG Xiao-wen, JI Jing, HUANG Shi-wen, CHENG Jian-ming

2023, 39(5): 452-466. doi: 10.14148/j.issn.1672-0482.2023.0452

[Abstract](227) [FullText HTML] (27) [PDF 3633KB](20)

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OBJECTIVE To characterize the chemical composition of the benchmark sample of Wenjing Decoction (WJT) by establishing fingerprints of WJT benchmark sample and conduct the common peaks identification and attribution. METHODS Agilent 5 TC-C₁₈ (2) column (250 mm×4.6 mm, 5 μm) was adopted, and acetonitrile (A)-0.1% formic acid aqueous solution (B) was used as the mobile phase for gradient elution. Assisted analysis through PeakView software, the chemical composition in the benchmark sample of the WJT was quickly identified, and the fingerprint of the benchmark sample of WJT was established by HPLC-UV and HPLC-ELSD. RESULTS A total of 122 compounds were analyzed and identified by the benchmark sample of WJT, and the relevant herbs was attributed. The HPLC-UV fingerprint of benchmark sample of WJT had 19 common peaks, and 9 chromatographic peaks of gallic acid, paeoniflorin, glycyrrhizic acid, liquiritin, cinnamaldehyde, paeonol, ferulic acid, ligustilide and β-ecdysone were identified by comparison of reference substance. There were 8 common peaks in the HPLC-ELSD fingerprint, and ginsenoside Rg₁, ginsenoside Re, and ginsenoside Rb₁ were identified by comparison of reference substance. The two fingerprints of HPLC-UV and HPLC-ELSD established could belong to all herbs of the whole prescription. CONCLUSION The method established by UV and ELSD is of high sensitivity, good stability and accuracy, which comprehensively reflects the overall characteristics of the benchmark sample of the WJT. The study provides a reliable basis for the establishment of quality standards for the benchmark sample of WJT.

Effect of Electroacupuncture Preconditioning on Activation of NEK7-NLRP3 Inflammasome in Lung Tissue of Rats with Sepsis Acute Lung Injury

ZHANG Yu-jie, XU Shu-wen, LIU Wen-mei, ZHANG Xin-fang, XIANG Shui-ying, JIANG Chuan-wei, WANG Yuan, LIU Zi-bing

2023, 39(5): 467-473. doi: 10.14148/j.issn.1672-0482.2023.0467

[Abstract](159) [FullText HTML] (22) [PDF 4912KB](16)

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OBJECTIVE To observe the effect of electroacupuncture (EA) pretreatment at "Zusanli" (ST 36) and "Chize" (LU 5) points on the activation of NEK7-NLRP3 inflammasome in the lung tissue of rats with sepsis acute lung injury (ALI), and to explore the protective effect and possible mechanism of EA pretreatment in septic ALI. METHODS According to the principle of randomization, 40 rats were equally divided into 4 groups, namely the control group, EA preconditioning+control group, model group and EA preconditioning+model group. The septic ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS). EA (4 Hz/20 Hz, 1-2 mA) was applied to bilateral ST 36 and LU 5 for 30 min, once a day for 7 consecutive days before modeling. The lung function of the rats was detected; HE staining was used to observe the pathological changes of the lung, and the degree of pulmonary edema in the left lung of rats was detected by the ratio of wet/dry weight of the lung; the secretions of inflammatory factors IL-1β and IL-18 in the plasma and lung tissue were measured by ELISA kits; the positive expression of ASC protein in the lung tissue of rats was observed by immunofluorescent staining; the expression of NEK7, NLRP3, Caspase-1 and IL-1β protein was assayed by Western blot. RESULTS Compared with the control group, the forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV_0.1), FEV_0.3, FEV_0.1/FVC, FEV_0.3/FVC were significantly decreased (P < 0.001); Inflammatory cell infiltration in the lung tissue was obvious and accompanied by congestion and edema, and the alveolar structure was ruptured; the ratio of W/D was significantly increased (P < 0.001); the contents of IL-1β and IL-18 in plasma and lung tissue were significantly increased (P < 0.001) while the ASC protein positive expression was increased significantly (P < 0.001); the expression levels of inflammasome-related proteins NEK7, NLRP3, Caspase-1 and IL-1β in lung tissue were significantly increased in the model group (P < 0.001). After EA intervention, the FVC, FEV_0.1, FEV_0.3, FEV_0.1/FVC, FEV_0.3/FVC were significantly increased (P < 0.05, P < 0.001), and the lung pathology has improved significantly. The other indicators mentioned above were significantly decreased in the EA preconditioning+model group (P < 0.05, P < 0.01, P < 0.001). CONCLUSION EA pretreatment can reduce pulmonary inflammatory response and improve lung function in septic ALI rats, which is relevant with inhibiting the activation of NEK7-NLRP3 inflammasome.

Mechanism of Zhuidu Formula Regulating c-JUN, Inhibiting Abnormal Glycosylation, and Reversing Drug Resistance of Triple Negative Breast Cancer

LI Yu-xuan, LIU Chun-liang, YUAN Qin, CHEN Ting, JIANG Yan-tao, YAO Fei, SUN Hua, HAO Min-xia, ZHANG Lu-rong, LIU Min

2023, 39(5): 474-482. doi: 10.14148/j.issn.1672-0482.2023.0474

[Abstract](197) [FullText HTML] (32) [PDF 1552KB](13)

Abstract:
OBJECTIVE To investigate the mechanism of reversal of drug resistance in triple negative breast cancer (TNBC) by Zhuidu Formula from the perspective of c-JUN-regulated glycosylation. METHODS MTT was used to detect cell proliferation. Western blot was used to detect the expression of c-JUN, β3GnT8, ppGalNAc-T1/2, CD147, and the drug resistance proteins BCRP and MDR1. MDA-MB-231/ADR cells overexpressing c-JUN were established using transfected c-JUN plasmids. In vivo experiments were performed by in situ transplantation of drug-resistant TNBC into nude mice. RESULTS Zhuidu Formula can significantly inhibit the proliferation of MDA-MB-231/ADR cells (P < 0.01), with a time-effect and dose-effect relationship. It also significantly inhibited the tumor weight of drug-resistant TNBC transplanted nude mice in situ (P < 0.01), reduced the expression of drug-resistant proteins BCRP and MDR1 (P < 0.01), and significantly decreased the expression of c-JUN, β3GnT8, ppGalNAc-T1/2, CD147 proteins (P < 0.01). After overexpression of c-JUN, the expression of β3GnT8, ppGalNAc T1/2, CD147, BCRP and MDR1 all showed an increase compared with the blank plasmid control group (P < 0.05, P < 0.01). The blank plasmid had no effect on the expression of the above proteins (compared with the blank control group, P > 0.05). Zhuidu Formula can significantly reduce the expression of the above proteins after overexpressing c-JUN, but the expression levels were still significantly higher than those in the blank plasmid group (P < 0.05, P < 0.01). CONCLUSION By acting on the regulatory factor c-JUN, Zhuidu Formula down-regulated the activation of β3GnT8 and ppGalNAc-T1/2, thereby inhibiting the glycosylation modification of CD147 and leading to the down-regulation of drug-resistant proteins BCRP and MDR1 to reverse TNBC drug resistance.

Mechanism of Yishen Xiezhuo Decoction in Treatment of Chronic Renal Failure by Inhibiting NKD2 Activity

GU Ming-jia, GAO Lei-ping, WEI Qing-xue, ZHU Ying, BAO Neng, ZHANG Hang, ZHU Jie-bin

2023, 39(5): 483-489. doi: 10.14148/j.issn.1672-0482.2023.0483

[Abstract](164) [FullText HTML] (21) [PDF 4232KB](19)

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OBJECTIVE To observe the effect of Yishen Xiezhuo Decoction on various renal function indexes by establishing a mouse model of chronic renal failure (CRF) and explore the mechanism by taking naked stratum corneum homolog 2 (NKD2) as the breakthrough point. METHODS The CRF model of mice was established by unilateral ureteral obstruction (UUO). After the last administration, the mice were killed. The morphology and weight of the mouse kidneys were observed and measured. The renal pathology was observed by Hematoxylin-Eosin and Masson staining. The degree of renal failure was evaluated by renal tubular injury score and renal fibrosis area measurement. Serum IL-1β, IL-6 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). The levels of BUN and SCr were detected by kits. Western blot was used to detect the protein expression of Collagen α1, FN1, α-SMA and NKD2. RESULTS Compared with the control group, the kidneys of the model group showed edema, reduced color and enlarged volume; renal mass index, renal tubular injury score, renal fibrosis area and Collagen α1 immunohistochemical expression increased significantly (P < 0.01). Serum levels of BUN, SCr, IL-6, IL-1β and TNF-α were increased significantly (P < 0.01), and the expression of kidney Collagen α1, FN1, α-SMA and NKD2 protein increased, too (P < 0.01). Compared with the model group, no significant difference was found on the scores of renal tubular injury in the low-dose group, but the renal weight index (P < 0.01), the level of renal fibrosis (P < 0.05) and the immunohistochemical expression of Collagen α1 (P < 0.05) decreased significantly. The levels of BUN, SCr, IL-6, IL-1β and TNF-α decreased significantly (P < 0.01), the protein expression of Collagen α1, FN1, α-SMA and NKD2 also decreased significantly (P < 0.01). Compared with the model group, the renal weight index, renal tubular injury scores and renal fibrosis area in the high-dose group were significantly reduced (P < 0.01); The levels of BUN, SCr, IL-6, IL-1β and TNF-α decreased significantly; the protein expression of kidney Collagen α1, FN1, α-SMA and NKD2 decreased significantly, too (P < 0.01). CONCLUSION Yishen Xiezhuo Decoction can down regulate the expression of NKD2, reduce the deposition of renal ECM, inhibit inflammatory responses, and delay the progress of CRF.

Differential Diagnosis and Treatment of Vocal Tic in Children by Mediating Qi Activities of Five Internal Organs

LIU Chang, ZHANG Ze-xin, WANG Shou-chuan

2023, 39(5): 490-494. doi: 10.14148/j.issn.1672-0482.2023.0490

[Abstract](173) [FullText HTML] (30) [PDF 962KB](28)

Abstract:
This paper summarized Professor Wang Shou-chuan's clinical experience of differential diagnosis and treatment of vocal tic in children by mediating qi activities of the five internal organs. It is believed that the lesion of vocal tic is located in the throat; the incidence of the disease is linked to the disorder of qi movements of the five internal organs. The pathogenic factors and the mechanism are wind invading the lung, spleen deficiency engendering phlegm, intense heart fire, kidney-yin deficiency, and then, inducing the liver wind. The clinical treatment is guided by the overall concept, with syndrome differentiation of the five internal organs as the main method. The method of soothing the lung, calming the liver, invigorating the spleen, clearing the heart fire and nourishing the kidney-yin can be separately applied in the light of the changes of pathogenesis, thus, the qi activities can be mediated, qi reversed and sound reduced. In order to achieve a better curative effect, pay attention to the children's mood and the clothing they are wearing in relation to temperature changes.

Historical Origin, Research Progress and Prospect of Calvatia Lilacina

CHEN Jun, YE Liang, HE Tang-tang, YANG Chen-xi, ZHAO Yu-rong, MIN Wen, DONG Jie, WANG Yi-wei

2023, 39(5): 495-500. doi: 10.14148/j.issn.1672-0482.2023.0495

[Abstract](323) [FullText HTML] (100) [PDF 666KB](23)

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Lasiosphaera seu Calvatia is a traditional Chinese medicine, which has been used in clinical practice for over two thousand years. In "Chinese Pharmacopoeia", it records that the dried fruit of Lasiosphaera seu Calvatia, including Lasiosphaera fenzlii Reich, Calvatia gigantea and Calvatia Lilacina. However, in various ancient books of Chinese medicine, only Calvatia Lilacina can be utilized as medicine. In this review paper, the application history, growth condition, chemical composition and pharmaceutical functions of Calvatia Lilacina were systematically reviewed and discussed. It was concluded that Calvatia Lilacina mainly used sporangium powder to promote wound healing. The major components of Calvatia Lilacina contain sterones, inorganic elements, volatile components and polysaccharides. Many studies reported that it can promote wound healing, prevent stress gastric ulcer and alcoholic liver injury together with antitumor ability. This paper provides a comprehensive review for further research, development and utilization of Calvatia Lilacina, leading to the research prospect of its application in wound healing under the guidance of TCM theory.

2023 Vol. 39, No. 5

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