Role of toll-like receptor 4/mutant myeloid differentiation primary response 88/nuclear factor kappa-B mediated inflammation in diabetes mellitus with Northwest dryness syndrome

doi:10.19852/j.cnki.jtcm.2024.05.004

Abstract

Abstract:

OBJECTIVE: To investigate the role of toll-like receptor 4 (TLR4)/mutant myeloid differentiation primary response 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway-mediated inflammation in diabetes mellitus with Northwest dryness syndrome.

METHODS: Rats were randomly divided into the normal control, type 2 diabetes (T2DM) model, Northwest dryness syndrome + T2DM (Northwest dryness), and simple internal dampness + T2DM (internal dampness) groups. Enzyme-linked immunosorbent assay was used to detect biochemical indexes and inflammatory factors. The histopathological observation was performed. Quantitative real-time polymerase chain reaction and Western blot analysis were used to detect the mRNA and protein expression levels, respectively.

RESULTS: Compared with the T2DM group, the glycosylated hemoglobin A1c, insulin, glucose tolerance, the homeostasis model assessment of insulin resistance, tumor necrosis factor-α, interleukin 1β, interleukin 16, malondialdehyde, blood lipid, alanine aminotransferase, and aspartate aminotransferase were significantly elevated in the internal dampness group. Their levels were significantly elevated in the Northwest dryness group than in the T2DM and internal dampness groups. The superoxide dismutase, glutathione peroxidase, liver glycogen, and organ-to-weight ratio were significantly declined in the internal dampness group and the Northwest dryness group than in the T2DM group. However, these levels were elevated in the Northwest dryness group than in the internal dampness group. Moreover, the mRNA expression levels of interferon regulatory factor 5 and NF-κB p65, and the protein expression levels of TLR4, MyD88, and NF-κB were significantly higher in the internal dampness and the Northwest dryness groups than the T2DM group. Additionally, the mRNA and protein levels were significantly higher in the Northwest dryness group than in the internal dampness group.

CONCLUSION: Northwest dryness syndrome-mediated TLR4/MyD88/NF-κB pathway and chronic inflammation might be associated with the occurrence and development of T2DM.

Key words: toll-like receptor 4, myeloid differentiation factor 88, NF-kappa B, inflammation, diabetes mellitus, Northwest dryness syndrome

DENG Deqiang, XIAO Yan, MA Dan, QIU Jinling, HAO Congli, WANG Di, ZHANG Miao. Role of toll-like receptor 4/mutant myeloid differentiation primary response 88/nuclear factor kappa-B mediated inflammation in diabetes mellitus with Northwest dryness syndrome[J]. Journal of Traditional Chinese Medicine, 2024, 44(5): 963-973.

Figures/Tables 11

Table 1 Analysis of fasting blood glucose in rats (mmol/L, $\bar{x}±s$)

Group	n	Before high-fat diet	High-fat diet for 2 weeks	High-fat diet for 4 weeks	2 weeks after the intervention	4 weeks after the intervention	6 weeks after the intervention	8 weeks after the intervention
Control	6	4.60±0.28	4.60±0.33	4.62±0.21	4.68±0.17	4.58±0.17	4.58±0.15	4.70±0.18
T2DM	6	4.68±0.33	6.07±0.37^ab	6.17±0.26^ab	18.00±0.94^abcd	19.37±1.17^abcde	20.15±1.27^abcde	20.53±0.75^abcde
Northwest dryness syndrome+T2DM	6	4.72±0.29	6.05±0.62^ab	6.22±0.31^ab	18.48±0.98^abcd	19.22±0.90^abcd	21.97±0.96^abcdefg	24.55±1.37^abcdefgi
Internal dampness syndrome+ 2DM	6	4.67±0.23	6.23±0.54^ab	6.32±0.29^ab	17.95±0.91^abcd	19.28±0.83^abcde	20.66±0.79^abcdegh	21.90±0.81^abcdefghi

Table 2 Changes of GHbA1c, insulin, and insulin resistance in rats ($\bar{x}±s$)

Group	n	GHbA1c (ng/mL)	Insulin (ng/mL)	HOMA-IR
Control	6	11.18±0.83	9.66±0.54	2.02±0.14
T2DM	6	24.34±1.98^a	25.53±2.36^a	23.32±2.48^a
Northwest dryness syndrome+T2DM	6	41.13±1.37^ab	32.09±1.71^ab	35.06±3.36^ab
Internal dampness syndrome+T2DM	6	32.24±3.10^abc	29.74±1.36^abc	28.98±2.37^abc

Table 3 Analysis of glucose tolerance in rats ($\bar{x}±s$)

Group	n	Fasting blood glucose (mmol/L)	Blood glucose at 30 min (mmol/L)	Blood glucose at 60 min (mmol/L)	Blood glucose at 120 min (mmol/L)	Glucose AUC (mg·h^-1·dL^-1)
Control	6	4.67±0.15	8.50±0.30^d	6.67±0.15	5.07±0.15^e	12.95±0.20
T2DM	6	20.53±0.67^a	26.73±1.12^ad	24.70±0.56^ac	22.57±1.06^aef	48.31±1.54^a
Northwest dryness syndrome+T2DM	6	25.43±0.71^ab	28.80±1.40^abd	32.13±1.45^abde	26.70±1.67^abef	58.21±2.79^ab
Internal dampness syndrome+T2DM	6	21.50±0.60^ac	25.13±0.93^acd	29.50±1.15^abcde	24.03±0.87^acdf	52.08±1.91^ac

Table 4 Analysis of insulin tolerance in rats ($\bar{x}±s$)

Group	n	Fasting blood glucose (mmol/L)	Blood glucose at 30 min (mmol/L)	Blood glucose at 60 min (mmol/L)	Blood glucose at 120 min (mmol/L)	Insulin AUC (mg·h^-1·dL^-1)
Control	6	4.60±0.10	2.50±0.10^d	2.93±0.15	3.80±0.20	4.82±0.06
T2DM	6	21.37±1.00^a	20.50±0.56^a	24.10±1.81^ade	22.50±0.96^a	33.27±1.54^a
Northwest dryness syndrome + T2DM	6	25.17±0.75^ab	22.47±0.85^ad	27.10±1.57^abe	25.33±0.76^abe	37.41±0.90^ab
Internal dampness syndrome + T2DM	6	21.53±0.74^ac	20.80±0.56^a	24.43±1.25^acde	22.13±0.93^acf	33.53±1.07^ac

Table 5 Changes of liver function (ALT and AST) and blood lipid (TC, TG, LDL, and HDL) levels in rats ($\bar{x}±s$)

Group	n	ALT (U/L)	AST (U/L)	TC (mmol/L)	TG (mmol/L)	LDL (mmol/L)	HDL (mmol/L)
Control	6	25.05±1.65	19.09±1.96	6.03±0.60	1.47±0.11	2.52±0.16	1.61±0.06
T2DM	6	42.37±3.07^a	33.78±2.19^a	14.16±1.54^a	4.65±0.58^a	5.89±0.41^a	1.19±0.06^a
Northwest dryness syndrome + T2DM	6	60.34±3.18^ab	51.66±2.61^ab	25.56±1.77^ab	7.87±0.50^ab	8.23±0.59^ab	0.56±0.07^ab
Internal dampness syndrome + T2DM	6	51.90±3.82^abc	45.71±4.62^ab	18.72±1.24^abc	5.21±0.46^ac	6.80±0.51^ac	0.87±0.08^abc

Figure 1 Pathological changes of pancreas, liver, perirenal adipose and epididymal adipose A: HE staining detection of the lesions of the pancreas in the four groups (magnification × 400). A1: control group; A2: T2DM group; A3: Northwest dryness group; A4: internal dampness group. B: HE staining detection of the lesions of the liver in the four groups (magnification × 400). B1: control group; B2: T2DM group; B3: Northwest dryness group; B4: internal dampness group.C: HE staining detection of the lesions of the perirenal adipose in the four groups (magnification × 400). C1: control group; C2: T2DM group; C3: Northwest dryness group; C4: internal dampness group. D: HE staining detection of the lesions of the epididymal adipose in the four group (magnification × 400). D1: control group; D2: T2DM group; D3: Northwest dryness group; D4: internal dampness group. E: PAS staining detection of the liver glycogen content in the four groups (magnification × 400). E1: control group; E2: T2DM group; E3: Northwest dryness group; E4: internal dampness group. Control group: rats were not treated; T2DM group: T2DM model was established; Northwest dryness syndrome + T2DM group: Northwest dryness syndrome and T2DM model were established; Internal dampness syndrome + T2DM group: Internal dampness syndrome and T2DM model were established. HE: hematoxylin-eosin; T2DM: type 2 diabetes mellitus.

Table 6 Analysis of organ-to-weight ratios in rats ($\bar{x}±s$)

Group	n	Body weight (g)	Pancreas (g)	Organ-to-weight ratio (%)	Liver (g)	Organ-to-weight ratio (%)	Perirenal adipose (g)	Organ-to-weight ratio (%)	Epididymal adipose (g)	Organ-to-weight ratio (%)
Control	6	421.44± 13.82	1.28± 0.07	0.30± 0.02	17.86± 1.09	4.24± 0.15	4.40± 0.18	1.05± 0.07	2.0±0.10	0.47± 0.04
T2DM	6	292.38± 16.43^a	0.73± 0.04^a	0.25± 0.03	11.92± 0.79^a	4.08± 0.08^a	2.32± 0.15^a	0.79±0.06	1.19±0.11^a	0.41± 0.04
Northwest dryness syndrome+T2DM	6	266.84± 10.63^ab	0.58± 0.03^a	0.22± 0.01	10.24± 0.70^ab	3.83± 0.14^ab	1.02± 0.11^ab	0.38± 0.05^ab	0.64±0.09^ab	0.24± 0.03^ab
Internal dampness syndrome+T2DM	6	277.24± 18.29^abc	0.66± 0.06^a	0.24± 0.02	10.92± 0.89^abc	3.94± 0.13^ab	1.57± 0.13^abc	0.57± 0.07^abc	0.86±0.06^a	0.31± 0.02^a

Figure 2 Changes in expression levels of IL-1β, TNF-α, and IL-16 in serum and liver tissues of rats by ELISA A: The levels of IL-1β, TNF-α, and IL-16 in serum of rats. A1: analysis of IL-1β expression; A2: analysis of TNF-α expression; A3: analysis of IL-16 expression. B: The levels of IL-1β, TNF-α, and IL-16 in liver tissues of rats. B1: analysis of IL-1β expression; B2: analysis of TNF-α expression; B3: analysis of IL-16 expression. Control group: rats were not treated (n = 6); T2DM group: T2DM model was established (n = 6); Northwest dryness syndrome + T2DM group: Northwest dryness syndrome and T2DM model were established (n = 6); Internal dampness syndrome + T2DM group: Internal dampness syndrome and T2DM model were established (n = 6). TNF-α: tumor necrosis factor-α; IL-1β: Interleukin 1 Beta; IL-6: Interleukin 16; T2DM: type 2 diabetes mellitus; ELISA: enzyme-linked immunosorbent assay. One-way analysis of variance and the least significance difference test were used for analysis. Data were expressed as mean ± standard deviation. Compared with the control group, aP<0.05; compared with the T2DM group, bP<0.05; and compared with the Northwest dryness group, cP<0.05.

Figure 3 Changes in the levels of SOD, MDA, liver glycogen, and GSH-PX in rats A: SOD level in rats from each group; B: MDA level in rats from each group; C: liver glycogen level in rats from each group; D: GSH-PX level in rats from each group. T2DM: type 2 diabetes mellitus; Control group: rats were not treated (n = 6); T2DM group: T2DM model was established (n = 6); Northwest dryness syndrome + T2DM group: Northwest dryness syndrome and T2DM model were established (n = 6); Internal dampness syndrome + T2DM group: Internal dampness syndrome and T2DM model were established (n = 6). SOD: superoxide dismutase; MDA: malondialdehyde; GSH-PX: glutathione peroxidase. One-way analysis of variance and the least significance difference test were used for analysis. Data were expressed as mean ± standard deviation. Compared with the control group, aP < 0.05; compared with the T2DM group, bP < 0.05; and compared with the Northwest dryness group, cP<0.05.

Table 7 Analysis of mRNA expression levels of IRF-5 and NF-κB p65 in rats

Group	n	IRF-5 (perirenal adipose tissue)	NF-κB p65 (perirenal adipose tissue)	IRF-5 (epididymal adipose tissue)	NF-κB p65 (epididymal adipose tissue)
Control	6	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
T2DM	6	3.81±0.47^a	3.64±0.20^a	3.67±0.30^a	3.71±0.06^a
Northwest dryness syndrome+T2DM	6	10.78±1.58^ab	14.61±1.05^ab	11.16±0.74^ab	15.34±0.29^ab
Internal dampness syndrome+T2DM	6	6.46±0.64^abc	7.22±0.34^abc	6.66±0.33^abc	7.70±0.93^abc

Figure 4 Changes in the protein expression levels of TLR4, NF-κB p65, and MyD88in the liver, perirenal adipose, and epididymal adipose tissues in rats A: TLR4, NF-κB p65, and MyD88 protein expression level in the liver tissue by Weston blot. A1: pictures of Western blot analysis of TLR4, NF-κB p65, and MyD88; A2: Western blot analysis of TLR4 expression; A3: Western blot analysis of NF-κB p65 MyD88 expression; A4: Western blot analysis of MyD88NF-κB p65 expression. B: TLR4, NF-κB p65, and MyD88 protein expression level in the perirenal adipose tissue by Weston blot. B1: pictures of Western blot analysis of TLR4, NF-κB p65, and MyD88; B2: Western blot analysis of TLR4 expression; B3: Western blot analysis of NF-κB p65 expression; B4: Western blot analysis of MyD88 expression. C: TLR4, NF-κB p65, and MyD88 protein expression level in the epididymal adipose tissue by Weston blot. C1: pictures of Western blot analysis of TLR4, NF-κB p65, and MyD88by Weston blot; C2: Western blot analysis of TLR4 expression; C3: Western blot analysis of NF-κB p65 expression; C4: Western blot analysis of MyD88 expression. Lane 1: Control; Lane 2: T2DM; Lane 3: northwest dryness syndrome; Lane 4: internal dampness. TLR4: toll-like receptor 4; MyD88: mutant myeloid differentiation primary response 88; NF-κB: nuclear factor kappa-B; T2DM: type 2 diabetes. Control group: rats were not treated (n = 6); T2DM group: T2DM model was established (n = 6); Northwest dryness syndrome + T2DM group: Northwest dryness syndrome and T2DM model were established (n = 6); Internal dampness syndrome + T2DM group: Internal dampness syndrome and T2DM model were established (n = 6). One-way analysis of variance and the least significance difference test were used for analysis. Data were expressed as mean ± standard deviation. Compared with the control group, aP<0.05; compared with the T2DM group, bP<0.05; and compared with the Northwest dryness group, cP<0.05.

References 35.

1.	Ala M, Jafari RM, Dehpour AR. Diabetes mellitus and osteoporosis correlation: challenges and hopes. Curr Diabetes Rev 2020; 16: 984-1001.
2.	Wang H, Li N, Chivese T, et al. IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by international association of diabetes in pregnancy study group's criteria. Diabetes Res Clin Pract 2022; 183: 109050.
3.	Li Y, Teng D, Shi X, et al. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ 2020; 369: m997.
4.	Fu L, Yang Y, Zhang T. Research progress on immune patho-genesis of type 2 diabetes. Zhong Guo Tang Niao Bing Za Zhi 2021; 29: 393-6.
5.	Hu Y. Research on the correlation between type 2 diabetes and northwest dryness syndrome and intervention treatment. Urumqi: Xinjiang Medical University; 2011: 1-56.
6.	Wang Y, Wang X, Zhao C. Expression characteristics of serum interleukin-17A and interleukin-10 in patients with Northwest dryness syndrome. J Tradit Chin Med 2016; 57: 1049-52.
7.	Zhou M. Overview of northwest dryness syndrome research. Shanghai Zhong Yi Yao Za Zhi 2005; 39: 43-5.
8.	Zhou M, Tao P. Preliminary study on desert dryness syndrome- research on health care of desert oil workers. J Tradit Chin Med 1997; 38: 493-6.
9.	Zhou M. Differentiation of pathogenic attribute of dryness. Xinjiang Zhong Yi Yao Za Zhi 2005; 23: 1-5.
10.	Wang Y, Zhou M. Discussion on the characteristics of Wu Ju Tong's treatment of dryness - literature study on the treatment of Northwest dryness syndrome. Xinjiang Zhong Yi Yao Za Zhi 2006; 24: 1-3.
11.	Jiang D, Zhou M. Discussion on the relationship between the etiology of dryness and cough-research on the etiology of Northwest dryness syndrome. Xinjiang Zhong Yi Yao 2006; 24: 7-9.
12.	Shatanati, Sun H, Zhou M. Preliminary study on the relationship between environmental geographical factors and sub-health status -background study on Northwest dryness syndrome. Xinjiang Zhong Yi Yao 2006; 24: 74-6.
13.	Hu Y, Huo B, Chen H, Zhou M. The influence of dryness on the pathogenesis of type 2 diabetes. Beijing Zhong Yi Yao Da Xue Xue Bao 2010; 17: 25-6.
14.	Zhou M, Song X, Shan L, et al. Epidemiological investigation and analysis of Northwest dryness syndrome among different ethnic residents in Xinjiang. Xinjiang Yi Ke Da Xue Xue Bao 2006; 29: 1034-8.
15.	Sharma D, Arora S, Banerjee A, Singh J. Improved insulin sensitivity in obese-diabetic mice via chitosan Nanomicelles mediated silencing of pro-inflammatory adipocytokines. Nanomedicine 2021; 33: 102357.
16.	Xiang Q, Jiang W, Yu R, et al. The effect of Zuogui compound on intestinal inflammation and mucosal barrier in type 2 diabetes mice based on the theory of "spleen based deficiency". Zhong Guo Mian Yi Xue Za Zhi 2020; 36: 667-71-76.
17.	Hu Y, Huo B, Zhou M. Observation on the therapeutic effect of Northwest dryness syndrome empirical prescriptions on type 2 diabetes. Liaoning Zhong Yi Yao Za Zhi 2012; 39: 1537-9.
18.	Ma T, Huang X, Zheng H, et al. SFRP2 improves mitochondrial dynamics and mitochondrial biogenesis, oxidative stress, and apoptosis in diabetic cardiomyopathy. Oxid Med Cell Longev 2021; 2021: 9265016.
19.	Shao Q, Meng L, Lee S, et al. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats. Cardiovasc Diabetol 2019; 18: 165. DOI PMID
20.	Wang L, Shi H, Zhou M. Observation on the duration of making animal model of Northwest dryness syndrome. Zhong Guo Zhong Yi Yao Za Zhi 2017; 32: 4585-8.
21.	Zhou Y, Zhang J. Research progress on animal models of internal dampness syndrome. Liaoning Zhong Yi Yao Da Xue Za Zhi 2018; 20: 141-4.
22.	Bao W, Sun H, Wu X, et al. Exploring anti-type 2 diabetes mellitus mechanism of Gegen Qinlian decoction by network pharmacology and experimental validation. Dis Markers 2022; 2022: 1927688.
23.	Zhao W, Chen L, Zhou H, et al. Protective effect of carvacrol on liver injury in type 2 diabetic db/db mice. Mol Med Rep 2021; 24: 741.
24.	Liu A, Ma L, Zhou G. Effect of Qinghao Biejia decoction and Northwest dryness syndrome empirical formula on perimenopausal anxiety rats with Yin deficiency and internal dryness. Zhong Guo Zhong Yi Ji Chu Yi Xue Za Zhi 2022; 28: 1085-8, 206.
25.	Deng D, Zhang Y, Ma D, Dilare A. Effects of Xiaoke Jianpi Capsule in the treatment of type 2 diabetes IR and TNF-α and IL-6. Xinjiang Zhong Yi Yao 2018; 36: 7-10.
26.	Zhu J, Sun L, Wang S, Zhang J, Wang M, Qiao F. Correlation between the serum interleukin-23, interleukin-17 and β cell function in adult patients with concealed autoimmune diabetes. Zhong Guo Yi Shi Za Zhi 2020; 22: 67-70.
27.	Deng L, Zhao X, Chen M, et al. Study on the correlation between plasma adiponectin, visfatin, leptin and resistin levels and the incidence of colonic polyps in pre diabetes population. Zhong Guo Nei Fen Bi Dai Xie Za Zhi 2018; 34: 997-1002.
28.	Wei Y, Li M, Yu J. Research progress on the relationship between chronic inflammation and insulin resistance. J Clin Pathol 2019; 39: 196-201.
29.	Lin Y, Jin W. Expression of GLUT1/4 in different glucose level and its effect on migration inhibitory factor in patients with type 2 diabetes mellitus. Zhong Guo Tang Niao Bing Za Zhi 2016; 24: 60-3.
30.	Crujeiras AB, Cordero P, Garcia-Diaz DF, Stachowska E, Gonzalez-Muniesa P. Molecular basis of the inflammation related to obesity. Oxid Med Cell Longev 2019; 2019: 5250816.
31.	He F, Huang Y, Song Z, et al. Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance. J Exp Med 2021; 218: e20201416.
32.	He L, Chen S. Effects of metformin combined with glimepiride on glucose and lipid metabolism, hemorheology and oxidative stress in elderly patients with type 2 diabetes. Zhong Guo Lao Nian Xue Za Zhi 2020; 40: 2283-6.
33.	Osorio FG, Barcena C, Soria-Valles C, et al. Nuclear lamina defects cause ATM-dependent NF-kappa B activation and link accelerated aging to a systemic inflammatory response. Genes Dev 2012; 26: 2311-24.
34.	Mitchell JP, Carmody RJ. NF-κB and the transcriptional control of inflammation. Int Rev Cell Mol Biol 2018; 335: 41-84. DOI PMID
35.	Deng D, Xu G, Zhou J, et al. Study on treatment of reinforcing spleen and dissipating dampness and promoting blood circulation (TRDP) on the function of pancreatic β cells in patients with type 2 diabetes mellitus. Liaoning Zhong Yi Yao Za Zhi 2015; 42: 1465-7.

[1]	LUO Kun, ZHONG Yumei, GUO Yanding, ZHANG Linlin, HU Danhui, MA Wenbin, YANG Xin, ZHOU Haiyan. Moxibustion inhibits the macrophage M1 polarization toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway by regulating T-cell immunoglobulin and mucin-containing protein-3 in rheumatoid arthritis [J]. Journal of Traditional Chinese Medicine, 2024, 44(6): 1227-1235.
[2]	ZHANG Guangshun, XU Xiaonan, XU Chuyun, LIAO Guanghui, XU Hao, LOU Zhaohuan, ZHANG Guangji. Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis [J]. Journal of Traditional Chinese Medicine, 2024, 44(5): 896-905.
[3]	YANG Chunyan, LUO Jia, PENG Weijie, DAI Weibo. Huaiyu pill (槐榆片) alleviates inflammatory bowel disease in mice via blocking toll like receptor 4/ myeloid differentiation primary response gene 88/ nuclear factor kappa B subunit 1 pathway [J]. Journal of Traditional Chinese Medicine, 2024, 44(5): 916-925.
[4]	JIN Hong, WANG Xinna, WANG Ruonan, LI Jinjian, YU Junchao, ZHAO Dexi, ZHAI Lu. Neuroprotective effect of Naochuxue prescription (脑出血方) on intracerebral hemorrhage: inhibition of autophagy via downregulating high mobility group box-1 [J]. Journal of Traditional Chinese Medicine, 2024, 44(5): 944-953.
[5]	GAO Jiaming, ZHANG Yehao, Chen Yuanyuan, JIN Long, ZHAO Jianfeng, GUO Hao, FU Jianhua. Qingfei Zhisou oral liquid (清肺止嗽口服液) alleviates fever-induced inflammation by regulating arachidonic acid and lysophospholipids metabolism and inhibiting hypothalamus transient receptor potential ion channels expression [J]. Journal of Traditional Chinese Medicine, 2024, 44(5): 954-962.
[6]	LI Yanjiao, HAO Linyao, LI Shuangyang, LUO Yanqi, WANG Juan, WANG Raoqiong, BAI Xue. Tongqiao Yizhi granule (通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats [J]. Journal of Traditional Chinese Medicine, 2024, 44(4): 680-687.
[7]	YANG Qinjun, YIN Dandan, WANG Hui, GAO Yating, WANG Xinheng, WU Di, TONG Jiabing, WANG Chuanbo, LI Zegeng. Uncovering the action mechanism of Shenqi Tiaoshen formula (参芪调肾方) in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification [J]. Journal of Traditional Chinese Medicine, 2024, 44(4): 770-783.
[8]	REN Li, HAI Yang, YANG Xue, LUO Xianqin. Yemazhui (Herba Eupatorii Lindleyani) ameliorates lipopolysaccharide-induced acute lung injury via modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flora in rats [J]. Journal of Traditional Chinese Medicine, 2024, 44(2): 303-314.
[9]	LI Liusheng, ZHAO Mingming, CHANG Meiying, SI Yuan, ZHAO Jinning, YANG Bin, ZHANG Yu. Protective effect of modified Huangqi Chifeng decoction (加味黄芪赤风汤) on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway [J]. Journal of Traditional Chinese Medicine, 2024, 44(2): 324-333.
[10]	ZHENG Xueying, GUO Liang, LAI Siyi, LI Fengyue, LIANG Mingli, LIU Wanting, MENG Chun, LIU Guanghui. Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway [J]. Journal of Traditional Chinese Medicine, 2024, 44(2): 268-276.
[11]	CHANG Fengjin, ZHOU Peng, LI Guoying, ZHANG Weizhi, ZHANG Yanyan, PENG Daiyin, CHEN Guangliang. Taohong Siwu decoction (桃红四物汤) ameliorates atherosclerosis in rats possibly through toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-κB signal pathway [J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 103-112.
[12]	JIN Tao, ZHOU Qian, SHEN Jichen, ZHANG Zhizhong, LIAN Xiaoyuan. Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model [J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 70-77.
[13]	LIU Huihui, FENG Jun, LIU Jianhe, CHENG Choufu, HU Guoheng. Efficacy of Jiangzhi Xiaoban tablet (降脂消斑片) on toll-like receptor 4/nuclear factor-kappa B/nod-like receptor protein 3 signaling pathway in mice with atherosclerosis induced by high-fat diet [J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 88-94.
[14]	JIN Shenyi, LIU Yahua, HAN Xu, CAI Mengjie, XU Jiatuo, LU Hao, CHEN Qingguang. Dark red tongue color formation caused by hyperglycemia is attributed to decreased blood flow of tongue tissue partially due to nuclear factor-kappa B pathway activation [J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1118-1125.
[15]	HENG Xianpei, WANG Zhita, YANG Liuqing, LI Liang, HUANG Suping. Dangua Fang (丹瓜方) regulating tricarboxylic acid cycle and respiratory chain and its mechanism in diabetic rats [J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1150-1159.

Home

Online First

Author Center

Reviewer Center

Issues

Announcement

About Us