The interaction between herbal medicine and GM can occur in multiple ways. One mechanism is by altering the composition and function of microorganisms, specifically bacteria
[9]. Another mechanism involves the action of metabolites derived from medicinal plants during the metabolic process in the body
[10]. Hence, the modulation of the GM through herbal medicines
[11] represents a novel frontier for developing medicines or drugs to treat obesity.
2. Results of the Search
In the preliminary stage of searching for articles, researchers retrieved 1094 records from the databases. After removing the duplicates, 790 titles and abstracts were screened in accordance with the inclusion criteria. Therefore, 14 publications were fully evaluated, 7 of which were excluded.
There was an attempt to contact the authors of one study with insufficient data on the GM results. Finally, seven publications from six studies were included in the review.
Figure 1 shows an overview of the screening procedure.
Figure 1. PRISMA study flow diagram for search up to April 2023.
3. Study Characteristics
Five studies were double-blind, parallel randomized clinical trials, and the other two had a crossover design
[12][13][14][15][14,15,16,17]. They were published between 2015/2023 and carried out in three countries: China, South Korea, and Spain. The individuals’ ages ranged from 20 to 75 years old. One study
[15][17] included only females, while the others encompassed both sexes. Two studies were limited to the overweight population. It is noteworthy that two complementary publications of the same study were found and were considered as one
[16][17][18,19].
The herbal medicines studied were
Moringa oleifera [14][16],
Punica granatum [16][17][18,19],
Scutellaria baicalensis [18][20],
Schisandra chinensis [15][17], and weight loss herbal intervention therapy consisting of five Chinese herbal medicines:
Ganoderma lucidum,
Coptis chinensis,
Astragalus membranaceus,
Nelumbo nucifera gaertn, and
Fructus aurantii (W-LHIT)
[12][14], and white common bean extract (WCBE)
[13][15].
In the study by Goméz-Martinéz et al.
[14][16],
Moringa oleifera was offered in 400 mg/capsules. The participants were instructed to take two capsules before the three main meals (breakfast, lunch, and dinner) for 12 weeks. Morbid obesity (body mass index, BMI > 35 kg/m
2) was used as an exclusion criterion.
The study by González-Sarrías et al.
[16][17][18,19] has a crossover design. Participants received a daily dose of 450 mg of
Punica granatum for three weeks, followed by a three-week washout period, and then another daily dose of 1800 mg for three weeks. Although the clinical trials treated the same population, they differ in their approaches and research methods regarding GM, being complementary in their results.
In the Shin et al. study
[18][20],
Scutellaria baicalensis was tested in association with the use of metformin in a crossover trial. The dosage given was 3.520 mg/day for eight weeks, followed by a wash-out period of four weeks, and a further eight weeks with a placebo. In both periods, the dosage of metformin was maintained according to the previous medical prescription of each participant. In the study conducted by Song et al.
[15][17], participants consumed
Schisandra chinensis in liquid form, provided in bags of 100 mL (two units) containing approximately 6700 mg of dry extract per day for a duration of eight weeks.
Extraction from white common beans (
Phaseolus vulgaris) was applied in the study of Feng
[13][15], being offered in doses of 1.5 g for each meal daily over the course of 4 months.
The other Chinese clinical trial by Cao
[12][14] prescribed capsules composed of five herbs (
Ganoderma lucidum,
Coptis chinensis,
Astragalus membranaceus,
Nelumbo nucifera gaertn, and
Fructus aurantii). The intervention group dosage was based on individual body weight, varying from 9 to 15 capsules a day for two months.
Table 1 describes the details of each study.
Table 1. Characteristics of the studies included in the systematic review.
14,15,18,19,20], while two others placed it as a secondary outcome
[14][15][16,17].
Table 2 describes the main finding of microbiota analysis.
Table 2. Changes of the GM following the administration of herbal medicines in overweight and obese individuals.
Article |
Intervention |
Microbiota Analysis Method |
GM Changes |
Cao [12] China | Cao [14] China |
9 to 15 capsules W-LHIT/day |
16S rRNA |
Increase in phylum | Verrucomicrobia | , and decrease in phylum | Proteobacteria | . Increase in genera | Akkermansia | and | Enterococcus. | Decrease in species | Eubacterium rectale | , | Haemophilus parainfluenzae | , and | Faecalibacterium prausnitzii | . |
Feng [13] China | Feng [15] China |
1.5 g WBCE before each meal/day |
16S rRNA |
Increase in genera | Anaerostipes | , | Bifidobacterium | , | Faecalibacterium | , | Faecalitalea Lactobacillus | , and | Romboutsia | , and decrease in genera | Adlercreutzia | ,
| Citrobacter | , | Cronobacter Enterobacteriaceae | , | Fusobacterium | , | Klebsiella | , and | Weissella | . |
Gómez-Martínez [14] | Gómez-Martínez [16] |
2.4 g dry extract MO/day 12 weeks |
16S rRNA |
No significant change in | Clostridium cluster IV | and in genera | Bifidobacterium | and | Lactobacillus | . No significant change in species | Blautia coccoides | , | Eubacterium rectale | , | Faecalibacterium prausnitzii | , and | Akkermansia muciniphila | . |
González-Sarrías [16] | González-Sarrías [18] |
0.45 g dry extract PG/day 3 weeks 1.8 g dry extract PG/day 3 weeks |
real-time qPCR |
Increase in genera | Gordonibacter | and | Bacteroides | . Increase in species | Escherichia coli | . |
González-Sarrías [17] | González-Sarrías [19] |
0.45 g dry extract PG/day 3 weeks 1.8 g dry extract PG/day 3 weeks |
16S rRNA |
Increase in phylum | Bacteroidetes | , and decrease in phylum | Firmicutes | . Increase in families | Bacteroidaceae | and | Porphyromonadaceae | , and decrease in families | Peptostreptococcaceae | , | Clostridiaceae | , | and Coriobacteriaceae | . Increase in genera | Bacteroides |
5.3 |
4.51 |
−2.10 [−7.29, 3.09] |
Insulin |
0.58 |
0.52 |
0.72 |
0.87 |
−0.14 [−0.95, 0.67] |
HbA1c |
0.05 |
0.13 |
0.03 |
0.14 |
0.02 [−0.13, 0.17] |
HOMA |
0.21 |
0.13 |
0.29 |
0.26 |
−0.08 [−0.31, 0.15] |
Weight |
−0.05 |
1.72 |
0.46 |
1.65 |
−0.51 [−2.42, 1.40] |
BMI |
0.01 |
0.49 |
0.19 |
0.48 |
−0.18 [−0.73, 0.37] |
Waist |
−0.22 |
1.28 |
0.54 |
1.28 |
−0.76 [−2.21, 0.69] |
Song 2015 (13/15) |
Change |
SD |
Change |
SD |
Mean difference (CI 95%) |
Glucose |
−1.31 |
5.86 |
1.0 |
6.1 |
−2.31 [−6.75, 2.13] |
Insulin |
−0.41 |
4.26 |
−0.64 |
5.98 |
0.23 [−3.58, 4.04] |
Cholesterol |
−1.69 |
24.30 |
−5.6 |
20.74 |
3.91 [−12.96, 20.78] |
HDL |
−1.15 |
8.97 |
−8.4 |
20.42 |
7.25 [−4.18, 18.68] |
TG |
−27.46 |
109.8 |
11.6 |
45.84 |
−39.06 [−103.10, 24.98] |
Weight |
−0.54 |
12.25 |
−0.8 |
8.72 |
0.26 [−7.73, 8.25] |
BMI |
−0.2 |
3.42 |
−0.33 |
2.82 |
0.13 [−2.21, 2.47] |
Waist |
−1.88 |
6.81 |
−1.36 |
7.6 |
−0.52 [−5.86, 4.82] |
%fat |
−2.39 |
4.19 |
−1.35 |
3.11 |
−1.04 [−3.81, 1.73] |
Author, Country |
Age (Years) |
BMI (kg/m | 2 | ) |
Gender |
Comorbities |
nB/N Endpoint (% Dropout) |
Intervention/Control |
Dosage |
Duration |
Cao [12] China | Cao [14] China |
18 to 60 |
32.25 ± 1.4 (intervention) 34.04 ± 2.5 (control) |
M: 24; F: 13 |
- |
37/40 (7.5%) |
W-LHIT |
9 to 15 capsules/day |
2 months |
Feng [13] China | Feng [15] China |
35 to 75 |
27.9 ± 0.4 (intervention) 25.1 ± 0.5 (control) |
M: 33; F: 50 |
Diabetes T2D |
83/96 (13.5%) |
WCBE |
1.5 g before each meal/day |
2 months |
Gómez-Martínez [14] Spain | Gómez-Martínez [16] Spain |
45 to 70 |
28.6 ± 3.8 (intervention) 29.4 ± 4.0 (control) |
M: 29; F: 36 |
Prediabetes |
73/65 (11.0%) |
Moringa |
| oleifera |
2.4 g/day |
, and a reduction in
Peptostreptococcaceae,
Clostridiaceae, and
Coriobacteriaceae.
The same phylum change was also observed in the clinical trial conducted by Song using
Schisandra Chinensis as an intervention
[15][17], which led to a subsequent reduction in the
Firmicutes/Bacteroidetes ratio. At the genus level, the intervention group showed an increase in
Akkermansia,
Roseburia,
Bacteroides,
Prevotella, and
Bifidobacterium, while only
Ruminococcus exhibited a decrease compared to the placebo group.
In the trial that combined
Scutellaria baicalensis with metformin
[18][20], there was an increase in the abundance of
Megamonas,
Mobilitalea,
Acetivibrio_g1,
Lactobacillus, and
Akkermansia. Conversely, a decrease in
Clostridium_g23,
Oscillibacter,
Alloprevotella, and
Bifidobacterium was observed. The
Weissella genus did not show any significant change in either the treatment or control groups.
The use of
Moringa oleifera [14][16] as a strategy for glycemic control did not find changes in the GM composition for Bacteroides,
Blautia coccoides,
Eubacterium rectale,
Clostridium cluster IV,
Bifidobacterium spp.,
Lactobacillus spp., and
Enterobacteriaceae. After the consumption of Moringa oleifera, the only bacterial group to show an increase was
Enterococcus spp. However, there were no significant changes observed in the levels of
Faecalibacterium prausnitzii and
Akkermansia muciniphila, which are considered bacterial species markers of gut health.
5. Anthropometric and Biomarkers Data
Researchers sought to identify outcomes related to the anthropometry and laboratory biomarkers of the selected clinical trials. As well as the GM data, the articles presented varied data. These divergences result in comparative limitations.
Table 3 presents the results for the parameters evaluated. When comparing the effects of the evaluated herbal medicines, no significant changes were observed in any variable.
Table 3. Anthropometric data and laboratory biomarkers of the studies included in the systematic review.
Study (N Intervention/N Control) |
Intervention |
Control |
|
Cao 2023 (18/19) |
Change |
SD |
Change |
SD |
Mean difference [CI 95%] |
Glucose |
−0.17 |
0.74 |
0.05 |
0.78 |
−0.12 [−0.61, 0.37] |
C-peptide |
−0.5 |
1.23 |
0.1 |
1.33 |
−0.40 [−1.22, 0.42] |
Insulin |
−3.87 |
9.78 |
−2.1 |
13.33 |
−1.77 [−9.28, 5.74] |
BMI |
−1.31 | and | Faecalibacterium | , and decrease in genera | Romboutsia | , | Anaerostipes | , | Dorea | , and | Clostridium sensu stricto | . No significant changes in bacterial diversity. |
Shin [18] | Shin [20] |
3.52 g dry extract SB/day 8 weeks |
16SrRNA |
Increase in genera | Lactobacillus | , | Weissella | , and | Akkermansia. | No significant changes in bacterial diversity. |
Song [15] | Song [17] |
6.7 g dry extract SC/day 12 weeks |
qPCR |
Increase in phylum | Bacteroidetes | , and decrease in phylum | Firmicutes | . Increase in genera | Akkermansia | , | Roseburia | , | Bacteroides | , | Prevotella | , and | Bifidobacterium | ; decrease in genus | Ruminococcus | . |
12 weeks |
González-Sarrías, [16][17] Spain | González-Sarrías, [18,19] Spain |
>40 |
28.5 ± 1.1 overweight 33.2 ± 3.3 obese |
M: 32; F: 17 |
- |
50/49 (2.0%) |
Punica |
| granatum |
0.45 g/day (3 weeks) 1.8 g/day (3 weeks) |
24 weeks (3 weeks of wash out between dosage) |
Shin [18] South Korea | Shin [20] South Korea |
20 to 75 |
25.62 ± 0.64
|
Clinical trials with W-LHIT
[12][14], WCBE
[13][15],
Punica granatum [17][19],
Scutellaria baicalensis [18][20], and
Moringa oleifera [14][16] used 16srRNA metagenomic technology for the analysis of GM. The other clinical trials
[15][16][17,18] collected data using the qPCR technique.
The study by González-Sarrías consisted of two separate publications, each utilizing different approaches for the analysis of the GM. In the first publication, which employed the qPCR technique
[16][18], there was a significant increase in the genera
Gordonibacter,
Bacteroides, and
Escherichia coli, alongside a reduction in lactic acid bacteria. The research on the GM has focused on bacteria involved in the conversion of secondary metabolites to urolithin, narrowing its spectrum of bacterial analysis.
The other publication
[17][19] sought to observe broader alterations in the GM with the use of
Punica granatum, in addition to verifying changes in the endotoxemia. For the interventional group, at the phylum level, there was an increase in
Bacteroidetes and a decrease in
Firmicutes. There was also an increase in
Bacteroides and
Faecalibacterium genera, with a reduction in
Romboutsia,
Anaerostipes,
Dorea, and
Clostridium sensu stricto. At the family level, there was an increase in
Bacteroidaceae and
Porphyromonadaceae
1.1 |
−0.88 |
0.88 |
−0.43 [−1.05, 0.19] |
Gomez-Martinez 2021 (31/34) |
Change |
SD |
Change |
SD |
Mean difference [CI 95%] |
Glucose |
−2.80 |
7.8 |
2.0 |
13.2 |
−4.80 [−10.02, 0.42] |
Insulin |
1.26 |
4.02 |
1.82 |
4.24 |
−0.56 [−2.57, 1.45] |
HbA1c |
−0.09 |
0.30 |
0.04 |
0.34 |
−0.13 [−0.29, 0.03] |
HOMA |
0.24 |
1.06 |
0.57 |
1.4 |
−0.33 [−0.93, 0.27] |
GLP |
−0.80 |
4.93 |
−1.4 |
4.75 |
0.60 [−1.76, 2.96] |
Ghrelin |
−47.0 |
66.58 |
−42.6 |
65.48 |
−4.40 [−36.55, 27.75] |
PYY |
−6.0 |
17.08 |
−7.33 |
19.61 |
1.33 [−7.59, 10.25] |
Shin 2019 (6/6) |
Change |
SD |
Change |
SD |
Mean difference (CI 95%) |
Glucose |
3.2 |
4.66 |
(intervention) 25.69 ± 0.62 (control) |
F and M |
Diabetes T2D |
17/12 (29.4%) |
Scutellaria |
| baicalensis |
3.52 g/day |
8 weeks (4 weeks of wash out) |
Song [15] South Korea | Song [17] South Korea |
25 to 45 |
29.99 ± 4.27 (intervention) 28.78 ± 3.47 (control) |
F |
- |
40/28 (30.0%) |
Schisandra chinensis |
6.7 g/day |
12 weeks |
4. Gut microbiota
GM research was highlighted as the main outcome in five articles
[12][13][16][17][18][
The study by González-Sarrías
[16][18] grouped the results of the surveyed population by type of urolithin (UM-A, UM-B, UM-0) presented in the urine after the clinical trial.
Only two studies reported adverse effects resulting from the consumption of herbal medicines. In the clinical trial conducted by Shin et al.
[18][20] using
Scutellaria baicalensis, one of the participants in the intervention group reported epigastric pain. The study by Cao et al.
[12][14] described two subjects with slight gastrointestinal reactions in the treatment group.