Improving glucose tolerance in obese rats: the role of Jinlida granules (津力达颗粒 ) in gut microbiota modulation

doi:10.19852/j.cnki.jtcm.2026.01.006

Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (1): 62-72.DOI: 10.19852/j.cnki.jtcm.2026.01.006

• Original Articles • Previous Articles Next Articles

Improving glucose tolerance in obese rats: the role of Jinlida granules (津力达颗粒 ) in gut microbiota modulation

LI Dongqi¹, WANG Tongxing²^,³, WANG Zixuan⁴, YAN Yihui¹, LI Jie¹, GU Jiaojiao¹, LI Cuiru¹, WANG Aili⁵, SUN Lingling⁶, MENG Yongjie¹, ZHANG Zeyu¹, HOU Yunlong²^,³(), GAO Huailin⁷()

1 Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050090, China
2 National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang 050035, China
3 Hebei Yiling Pharmaceutical Research Institute, Key Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Diseases), Shijiazhuang 050035, China
4 Graduate School, Hebei Medical University, Shijiazhuang 050017, China
5 Department of Medical Oncology, Hebei Yiling Hospital, Shijiazhuang 050091, China
6 Graduate School, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China
7 Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050090, China; Endocrinology Department, Hebei Yiling Hospital, Shijiazhuang 050091, China

Received:2024-08-22 Accepted:2025-05-28 Online:2026-02-15 Published:2026-01-28
Contact: HOU Yunlong, National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang 050035, China; Hebei Yiling Pharmaceutical Research Institute, Key Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Diseases), Shijiazhuang 050035, China, houyunlonghrb@hotmail.com; GAO Huailin, Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050090, China; Endocrinology Department, Hebei Yiling Hospital, Shijiazhuang 050091, China, gaohuailin@126.com;Telephone: +86-18503210603
About author:LI Dongqi and WANG Tongxing are co-first authors and contributed equally to this work
Supported by:
National Key Research and Development Program 'Modernization Research of Traditional Chinese Medicine': Cardiovascular Event Chain (Metabolic Syndrome, Atherosclerosis, Myocardial Infarction, Arrhythmia, Heart Failure)(2017YFC700500);Key R&D Program of Hebei: Traditional Chinese Medicine Innovation Project: Clinical Research on the Treatment of Diabetes Foot with Collateral Drugs and the Mechanism of Its Influence on Collateral Vessel Reconstruction(223777155D);Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine: Clinical Study on Jinlida Granules in Treating Intestinal Dysfunction of diabetes and Its Effect on Short Chain Fatty Acids(2023179);Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine: Clinical Study on Tongluo Therapy for Diabetes Foot and Its Influence on Microcirculation(2018200)

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Abstract

Abstract:

OBJECTIVE: To investigate the effects of Jinlida granules (津力达颗粒, JLD) on body weight, glucose tolerance, intestinal inflammation and barrier function in high-fat diet (HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism.

METHODS: Sprague-Dawley rats were divided into control, HFD, low-dose JLD (L-JLD), high-dose JLD (H-JLD), and sitagliptin groups. The rats, with the exception of those in the control group, were fed a HFD to establish an obesity model while simultaneously receiving 0.5% carboxymethyl cellulose, L-JLD, H-JLD or sitagliptin for 25 weeks. We assessed body weight, conducted oral glucose tolerance tests, and analysed faecal samples using metagenomic sequencing. Haematoxylin-eosin (HE), Masson and immunohistochemical (IHC) staining were employed to evaluate histological changes in the colon tissue. Immunofluorescence (IF) staining was used to measure the expression levels of Zonula occludens-1 (ZO-1) and Claudin-1 in colon tissue. The colon tissue was also subjected to transcriptomic evaluation.

RESULTS: JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats. It alleviated colonic tissue damage, decreased collagen deposition, inhibited macrophage infiltration, and increased the expression of the tight junction proteins ZO-1 and Claudin-1. Metagenomic analysis revealed JLD-induced shifts in the gut microbiota composition (increasing the abundance of Turicibacter, Faecalibaculum, Coriobacteriaceae and Lactobacillus reuteri), enriching beneficial bacteria and metabolic pathways (increasing the biosynthesis of various secondary metabolites, ascorbate and aldarate metabolism, oxidative phosphorylation, C5-branched dibasic acid metabolism and beta-alanine metabolism). Transcriptomic analysis revealed downregulation of inflammatory and immune pathways (inhibition of the tumour necrosis factor signalling pathway, advanced glycation end products-receptor for advanced glycation end products signalling pathway, toll-like receptor signalling pathway, and interleukin-17 signalling pathway), suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function.

CONCLUSIONS: JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats. These benefits are likely mediated through the modulation of the gut microbiota, the suppression of intestinal inflammation, the enhancement of barrier function, and the attenuation of proinflammatory pathways. Our findings offer novel insights into the therapeutic potential of JLD, emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.

Key words: Jinlida granules, obesity, gut microbiota, intestinal barrier, intestinal inflammation, glucose tolerance

LI Dongqi, WANG Tongxing, WANG Zixuan, YAN Yihui, LI Jie, GU Jiaojiao, LI Cuiru, WANG Aili, SUN Lingling, MENG Yongjie, ZHANG Zeyu, HOU Yunlong, GAO Huailin. Improving glucose tolerance in obese rats: the role of Jinlida granules (津力达颗粒 ) in gut microbiota modulation[J]. Journal of Traditional Chinese Medicine, 2026, 46(1): 62-72.

Figures/Tables 8

Table 1 JLD reduced body weight gain (g, $\bar{x} \pm s$)

Group	n	0 week	4 weeks	8 weeks	12 weeks	16 weeks	20 weeks	24 weeks
Control	5	751±100	782±136	816±143	810±143	845±135	844±127	876±129
HFD	5	738±61	821±65	875±129	876±92	940±66	970±70	1032±80^c
L-JLD	7	727±93	751±104	774±95^a	791±102	813±99^a	861±105	898±115
H-JLD	7	702±68	742±81	747±75^a	763±85^a	790±93^a	799±108^b	827±128^b
Sitagliptin	7	738±52	790±63	815±86	840±92	888±106	907±110	950±124

Table 2 JLD improved glucose tolerance (mmol/L, $\bar{x} \pm s$)

Group	n	0 min	30 min	60 min	120 min
Control	5	6.38±0.63	9.42±1.62	9.50±1.11	8.52±1.19
HFD	5	6.20±0.79	8.22±1.21	9.70±1.37	9.90±1.33^c
L-JLD	7	6.06±0.94	7.67±1.16^a	8.14±0.70^a	8.46±1.13^a
H-JLD	7	5.86±0.27	7.36±0.83^b	8.66±0.81	7.87±0.95^b
Sitagliptin	7	6.00±0.37	7.09±0.97^b	7.69±1.23^b	7.93±0.60^b

Figure 1 JLD improved the histopathology of colon tissues and ameliorated inflammation in colon tissues A: representative HE staining images of colon tissues (× 5 and × 20, scale bar = 500 μm). Intestinal epithelial cells are indicated with black arrows and the spacing of colonic glands is indicated with red arrows; B: Representative Masson staining of colon sections (× 10, scale bar = 250 μm); C: representative immunohistochemical staining for F4/80 in colon sections (× 20 and × 60, scale bar = 100 μm). A1, A6，B1, C1, C6: Control group; A2, A7, B2, C2, C7: HFD group; A3, A8, B3, C3, C8: L-JLD group; A4, A9, B4, C4, C9: H-JLD group; A5, A10, B5, C5, C10: Sitagliptin group. Control: fed with normal food + the same volume of 5% CMC was given by gavage for 25 weeks; HFD: fed with HFD + the same volume of 5% CMC was given by gavage for 25 weeks; L-JLD: fed with HFD + received an intragastric administration of JLD at a dosage of 1.5 g·kg?1·d?1 for 25 weeks ; H-JLD: fed with HFD + received an intragastric administration of JLD at a dosage of 3 g·kg?1·d?1 for 25 weeks ; Sitagliptin: fed with HFD + received an intragastric administration of sitagliptin at a dosage of 10 mg·kg?1·d?1 for 25 weeks. HFD: high-fat diet; L-JLD: low dose Jinlida; H-JLD: high dose Jinlida; HE: hematoxylin-eosin; CMC: carboxymethyl cellulose.

Table 3 The proportion of collagen fibre area and F4/80 positive area in the colon tissue of rats in each group (%,$\bar{x} \pm s$)

Group	n	Collagen fibre	F4/80
Control	4	8.85±2.20	0.917±0.144
HFD	4	14.26±2.54^a	1.186±0.117^c
L-JLD	4	9.34±1.94^b	0.775±0.164^b
H-JLD	4	9.03±1.42^b	0.774±0.050^b
Sitagliptin	4	9.67±1.05^b	0.843±0.105^b

Figure 2 JLD protected the intestinal barrier in HFD-induced obese rats A: immunofluorescence of colonic ZO-1 (× 40 and × 80, scale bar = 40 μm); B: immunofluorescence of colonic Claudin-1 (× 40, scale bar = 40 μm). A1, B1: Control group; A2, B2: HFD group; A3, B3: L-JLD group; A4, B4: H-JLD group; A5, B5: Sitagliptin group. Control: fed with normal food + the same volume of 5% CMC was given by gavage for 25 weeks; HFD: fed with HFD + the same volume of 5% CMC was given by gavage for 25 weeks; L-JLD: fed with HFD + received an intragastric administration of JLD at a dosage of 1.5 g·kg?1·d?1 for 25 weeks; H-JLD: fed with HFD + received an intragastric administration of JLD at a dosage of 3 g·kg?1·d?1 for 25 weeks; Sitagliptin: fed with HFD + received an intragastric administration of sitagliptin at a dosage of 10 mg·kg?1·d?1 for 25 weeks. JLD: Jinlida granules; HFD: high-fat diet; ZO-1: zonula occludens-1; CMC: carboxymethyl cellulose; L-JLD: low dose Jinlida; H-JLD: high dose Jinlida.

Table 4 Average fluorescence intensity of ZO-1 and Claudin-1 protein expression in colon tissue of rats in each group ($\bar{x} \pm s$)

Group	n	ZO-1	Claudin-1
Control	4	101.1±5.0	106.1±11.3
HFD	4	71.0±6.7^a	52.8±9.0^a
L-JLD	4	87.4±9.1^b	87.7±9.3^b
H-JLD	4	87.7±6.1^b	108.0±7.4^c
Sitagliptin	4	91.5±1.0^b	85.9±9.6^b

Figure 3 Analysis of the colon tissue transcriptome from the H-LJD and HFD groups A: volcano plot showing the DEGs in the H-JLD/HFD comparison; B: heatmap for the H-JLD/HFD comparison. C: top 20 KEGG pathways for the H-JLD/HFD comparison. The genes behind each bar represent the DEGs involved in the pathway. The red and green genes represent upregulated and downregulated DEGs in the H-JLD/HFD comparison, respectively. HFD: fed with HFD + the same volume of 5% CMC was given by gavage for 25 weeks; H-JLD: fed with HFD + received an intragastric administration of JLD at a dose of 3 g·kg?1·d?1 for 25 weeks; DEGs: differentially expressed genes; HFD: high-fat diet; H-JLD: high dose Jinlida. KEGG: kyoto encyclopedia of genes and genomes; CMC: carboxymethyl cellulose; FDR: false discovery rate; FC: fold change. DEGs were selected with the following conditional thresholds: q value (FDR) < 0.05 and absolute FC ≥ 2. n = 5 for each group.

Figure 4 JLD altered the diversity and composition of the gut microbiota in HFD-induced obese rats A: alpha-diversity measured by the Simpson index; B: NMDS plot based on the Bray-Curtis index; C: phylum-level distribution of the gut microbiota; D: relative abundances of Bacteroides species; E: genus-level distribution of the gut microbiota; F: relative abundances of Turicibacter; G: relative abundances of Faecalibaculum; H: relative abundances of Coriobacteriaceae; I: relative abundances of Lactobacillus reuteri; J: LDA at the genus and species levels. Control: fed with normal food + the same volume of 5% CMC was given by gavage for 25 weeks; HFD: fed with HFD + the same volume of 5% CMC was given by gavage for 25 weeks; H-JLD: fed with HFD + received an intragastric administration of JLD at a dose of 3 g·kg?1·d?1 for 25 weeks. JLD: Jinlida granules; HFD: high-fat diet; NMDS: nonmetric multidimensional scaling; CMC: carboxymethyl cellulose; LDA: linear discriminant analysis. Statistical analyses were measured using the least significant difference test and Tamhane's T2 test for pairwise comparisons between groups. Compared with control group, aP < 0.001, cP < 0.05; compared with HFD group, bP < 0.001, dP < 0.05. Control and HFD groups, n = 5; H-JLD group, n = 6.

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