Effects of Shenlian formula (参连方) on microbiota and inflammatory cytokines in adults with type 2 diabetes: a double-blind randomized clinical trial

doi:10.19852/j.cnki.jtcm.20230608.003

Abstract

Abstract:

OBJECTIVES: To observe the efficacy of Shenlian formula (SL formula, 参连方), which consist of Huanglian (Rhizoma Coptidis) and Renshen (Radix Ginseng), in the treatment of type 2 diabetes mellitus (T2DM) and explore the effects on gut microbiota and serum inflammatory cytokines.

METHODS: In a double-blind, randomized, placebo-controlled parallel-group clinical trial, 31 adults with T2DM were randomly allocated to receive the SL formula or placebo for 12 weeks. Body mass index (BMI), blood lipid indices, glycemic biomarkers including glycated hemoglobin (HbA1C), fasting plasma glucose (FPG), postprandial blood glucose (PBG), fasting insulin levels (FIL), fasting C-peptide (C-P), homoeostasis model assessment for insulin resistance (HOMA-IR) and inflammatory cytokines were assessed at baseline and 12 weeks. The contents of gut microbiota were determined by pyrosequencing of the V3-V4 regions of 16S rRNA genes.

RESULTS: Sixteen cases were allocated in the treatment group and 15 in the placebo group. Compared with the placebo, SL formula resulted in a higher significant reduction in PBG [(?1.318 ± 0.772) vs (?0.008 ± 1.404) mmol/L, P = 0.003], BMI [(?0.611 ± 0.524) vs (0.957 ± 2.212) kg/m², P = 0.01], FIL [(?1.627 ± 6.268) vs (3.976 ± 6.85) μIU/mL, P = 0.02], HOMA-IR [(?0.530 ± 1.461) vs (1.511 ± 2.288), P = 0.006], and C-reactive protein (CRP) [(?1.307 ± 0.684) vs (0.828 ± 0.557) mg/L, P = 0.04]. In terms of gut microbiota, compared with the placebo, the SL formula resulted in a significant decrease in species richness and evenness.

CONCLUSIONS: The SL formula showed the efficacy to improve postprandial blood glucose, insulin resistance, BMI and CRP levels. In addition, it could reduce the total number, richness and evenness of species, meanwhile increase the abundance of probiotics to modulate the structure of gut microbiota in patients with T2DM. However, further studies are required for exploring the deeper mechanism of TCM on gut microbiota.

Key words: Huanglian (Rhizoma Coptidis), Renshen (Radix Ginseng), diabetes mellitus, type 2, gut microbiota, cytokines, clinical trial

JIANG Li, FU Qiang, WANG Shidong, ZHAO Jinxi, CHEN Yu, LI Jiayue, XIAO Yonghua, HUANG Weijun, SUN Ruixi, XIAO Yao, SHEN Aijia, WANG Junheng, LIU Jiangteng, FU Xiaozhe, LI Yuanyuan, ZHAO Yu, XUE Taiqi. Effects of Shenlian formula (参连方) on microbiota and inflammatory cytokines in adults with type 2 diabetes: a double-blind randomized clinical trial[J]. Journal of Traditional Chinese Medicine, 2023, 43(4): 760-769.

Figures/Tables 6

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Item		Total (n = 31)	Sl group (n = 16)	Placebo group (n = 15)	P value
Age (years)		54.8±10.6	52.4±8.4	56.9±12.4	0.38
Gender [n (%)]	Male	15 (48.4)	8 (50.0)	7 (46.7)	0.87
	Female	16 (51.6)	8 (50.0)	8 (53.3)
Course of disease (years)		7.2±0.4	6.9±2.3	7.5±2.6	0.55
Weight (kg)		72.5±11.7	73.2±12.0	71.8±11.8	0.74

Item		Total (n = 31)	Sl group (n = 16)	Placebo group (n = 15)	P value
Age (years)		54.8±10.6	52.4±8.4	56.9±12.4	0.38
Gender [n (%)]	Male	15 (48.4)	8 (50.0)	7 (46.7)	0.87
	Female	16 (51.6)	8 (50.0)	8 (53.3)
Course of disease (years)		7.2±0.4	6.9±2.3	7.5±2.6	0.55
Weight (kg)		72.5±11.7	73.2±12.0	71.8±11.8	0.74

Item		Group	n	At baseline	At 12 weeks	Baseline-week 12	P values^a	P values between groups^b
Glycemic biomarkers	HbA1c (%)	SL formula	16	9.035±1.933	6.950±1.370^a	2.085±1.822	<0.001	0.97
	HbA1c (%)	Placebo	15	8.960±2.329	6.853±0.795^a	2.107±2.081	0.002
	FPG (mmol/L)	SL formula	16	6.964±1.290	6.597±1.732	0.367±1.323^b	0.28	0.04
	FPG (mmol/L)	Placebo	15	5.456±1.399	6.317±1.543	—0.861±1.914	0.10
	PBG (mmol/L)	SL formula	16	9.660±0.906	8.342±1.081^a	1.318±0.772^c	<0.001	0.003
	PBG (mmol/L)	Placebo	15	9.075±1.720	9.067±1.074	0.008±1.404	0.98
	FIL (μIU/mL）	SL formula	16	16.962±24.341	15.335±19.176	1.627±6.268^b	0.32	0.02
	FIL (μIU/mL）	Placebo	15	8.541±4.861	12.517±9.500	—3.976±6.855	0.32
	C-P (ng/mL)	SL formula	16	2.577±2.356	2.537±1.732	0.040±0.872	0.85	0.62
	C-P (ng/mL)	Placebo	15	1.833±0.856	1.950±1.054	—0.117±0.888	0.61
	HOMA-IR	SL formula	16	5.682±8.608	5.152±7.948	0.530±1.461^c	0.17	0.006
	HOMA-IR	Placebo	15	2.093±1.331	3.604±2.745	—1.511±2.288	0.02
Blood lipid indices	TG (mmol/L)	SL formula	16	1.780±1.210	1.633±1.213	0.147±1.143	0.62	0.40
	TG (mmol/L)	Placebo	15	1.053±0.499	1.185±0.460	—0.132±0.551	0.37
	LDL-C (mmol/L)	SL formula	16	2.572±0.990	2.239±0.899	0.333±1.103	0.24	0.35
	LDL-C (mmol/L)	Placebo	15	1.997±0.835	2.025±0.730	—0.028±1.029	0.92
	BMI (kg/m²)	SL formula	16	26.504±3.657	25.893±3.624^a	0.611±0.524^c	<0.001	0.01
	BMI (kg/m²)	Placebo	15	25.718±3.517	26.675±3.623	—0.957±2.212	0.12
Inflammatory Cytokines	TNF-α (pg/mL)	SL formula	16	672.632±78.018	595.746±68.302^a	76.886±46.244	<0.001	0.26
	TNF-α (pg/mL)	Placebo	15	668.096±88.240	610.399±68.329^a	57.697±41.381	<0.001
	IL-6 (pg/mL)	SL formula	16	55.380±5.129	47.281±6.223^a	8.099±5.883	<0.001	0.10
	IL-6 (pg/mL)	Placebo	15	52.651±5.957	47.509±5.545^a	5.142±2.845	<0.001
	CRP (mg/L)	SL formula	16	6.129±1.110	4.822±1.316^a	1.307±0.684^b	<0.001	0.04
	CRP (mg/L)	Placebo	15	5.337±1.334	4.509±1.230^a	0.828±0.557	<0.001
Safety indicators	ALT (mmol/L)	SL formula	16	19.131±11.522	17.944±7.914	1.187±9.523	0.62	0.39
	ALT (mmol/L)	Placebo	15	17.900±6.264	21.420±19.112	—3.520±19.437	0.49
	AST (mmol/L)	SL formula	16	17.763±7.168	16.056±5.233	1.707±7.413	0.37	0.77
	AST (mmol/L)	Placebo	15	18.220±5.808	17.253±7.415	0.967±6.524	0.58
	BU (mmol/L)	SL formula	16	4.641±1.408	4.728±1.650	—0.087±1.333	0.78	0.50
	BU (mmol/L)	Placebo	15	4.217±1.271	4.707±1.603	—0.49±1.892	0.33
	Cr (μmol/mL)	SL formula	16	52.994±11.469	51.438±11.708	1.556±9.921	0.54	0.49
	Cr (μmol/mL)	Placebo	15	53.313±14.676	54.787±9.865	—1.474±14.183	0.70

Item		Group	n	At baseline	At 12 weeks	Baseline-week 12	P values^a	P values between groups^b
Glycemic biomarkers	HbA1c (%)	SL formula	16	9.035±1.933	6.950±1.370^a	2.085±1.822	<0.001	0.97
	HbA1c (%)	Placebo	15	8.960±2.329	6.853±0.795^a	2.107±2.081	0.002
	FPG (mmol/L)	SL formula	16	6.964±1.290	6.597±1.732	0.367±1.323^b	0.28	0.04
	FPG (mmol/L)	Placebo	15	5.456±1.399	6.317±1.543	—0.861±1.914	0.10
	PBG (mmol/L)	SL formula	16	9.660±0.906	8.342±1.081^a	1.318±0.772^c	<0.001	0.003
	PBG (mmol/L)	Placebo	15	9.075±1.720	9.067±1.074	0.008±1.404	0.98
	FIL (μIU/mL）	SL formula	16	16.962±24.341	15.335±19.176	1.627±6.268^b	0.32	0.02
	FIL (μIU/mL）	Placebo	15	8.541±4.861	12.517±9.500	—3.976±6.855	0.32
	C-P (ng/mL)	SL formula	16	2.577±2.356	2.537±1.732	0.040±0.872	0.85	0.62
	C-P (ng/mL)	Placebo	15	1.833±0.856	1.950±1.054	—0.117±0.888	0.61
	HOMA-IR	SL formula	16	5.682±8.608	5.152±7.948	0.530±1.461^c	0.17	0.006
	HOMA-IR	Placebo	15	2.093±1.331	3.604±2.745	—1.511±2.288	0.02
Blood lipid indices	TG (mmol/L)	SL formula	16	1.780±1.210	1.633±1.213	0.147±1.143	0.62	0.40
	TG (mmol/L)	Placebo	15	1.053±0.499	1.185±0.460	—0.132±0.551	0.37
	LDL-C (mmol/L)	SL formula	16	2.572±0.990	2.239±0.899	0.333±1.103	0.24	0.35
	LDL-C (mmol/L)	Placebo	15	1.997±0.835	2.025±0.730	—0.028±1.029	0.92
	BMI (kg/m²)	SL formula	16	26.504±3.657	25.893±3.624^a	0.611±0.524^c	<0.001	0.01
	BMI (kg/m²)	Placebo	15	25.718±3.517	26.675±3.623	—0.957±2.212	0.12
Inflammatory Cytokines	TNF-α (pg/mL)	SL formula	16	672.632±78.018	595.746±68.302^a	76.886±46.244	<0.001	0.26
	TNF-α (pg/mL)	Placebo	15	668.096±88.240	610.399±68.329^a	57.697±41.381	<0.001
	IL-6 (pg/mL)	SL formula	16	55.380±5.129	47.281±6.223^a	8.099±5.883	<0.001	0.10
	IL-6 (pg/mL)	Placebo	15	52.651±5.957	47.509±5.545^a	5.142±2.845	<0.001
	CRP (mg/L)	SL formula	16	6.129±1.110	4.822±1.316^a	1.307±0.684^b	<0.001	0.04
	CRP (mg/L)	Placebo	15	5.337±1.334	4.509±1.230^a	0.828±0.557	<0.001
Safety indicators	ALT (mmol/L)	SL formula	16	19.131±11.522	17.944±7.914	1.187±9.523	0.62	0.39
	ALT (mmol/L)	Placebo	15	17.900±6.264	21.420±19.112	—3.520±19.437	0.49
	AST (mmol/L)	SL formula	16	17.763±7.168	16.056±5.233	1.707±7.413	0.37	0.77
	AST (mmol/L)	Placebo	15	18.220±5.808	17.253±7.415	0.967±6.524	0.58
	BU (mmol/L)	SL formula	16	4.641±1.408	4.728±1.650	—0.087±1.333	0.78	0.50
	BU (mmol/L)	Placebo	15	4.217±1.271	4.707±1.603	—0.49±1.892	0.33
	Cr (μmol/mL)	SL formula	16	52.994±11.469	51.438±11.708	1.556±9.921	0.54	0.49
	Cr (μmol/mL)	Placebo	15	53.313±14.676	54.787±9.865	—1.474±14.183	0.70

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