{"id":67903,"date":"2025-09-30T10:46:37","date_gmt":"2025-09-30T10:46:37","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=67903"},"modified":"2025-10-14T04:41:59","modified_gmt":"2025-10-14T04:41:59","slug":"therapeutic-potential-of-red-ginger-zingiber-officinale-var-rubrum-bioactive-compounds-in-obesity-associated-metabolic-parameters-of-wistar-rats","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol18no3\/therapeutic-potential-of-red-ginger-zingiber-officinale-var-rubrum-bioactive-compounds-in-obesity-associated-metabolic-parameters-of-wistar-rats\/","title":{"rendered":"Therapeutic Potential of Red Ginger (Zingiber officinale var. Rubrum) Bioactive Compounds in Obesity-Associated Metabolic Parameters of Wistar Rats."},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Obesity is an escalating global health concern that is strongly linked to insulin resistance and metabolic disturbances, including hyperglycemia, hypertriglyceridemia, and increased free fatty acid levels. \u00a0All of these factors\u00a0 increase the risk of metabolic syndrome and cardiometabolic diseases. Mechanistic studies and reviews suggest that ginger products and bioactive compounds can modulate immunometabolic pathways associated with adipogenesis, adipose tissue inflammation, and glucose homeostasis.1<\/sup><\/p>\n

Red ginger\u00a0 is a commonly consumed ginger variety in Indonesia and is reported to have a relatively high phenolic and vanilloid content (including gingerols and shogaols) compared to other varieties, potentially exhibiting potent antioxidant, anti-inflammatory, and metabolic activities. This makes red ginger an attractive candidate as a natural agent for addressing metabolic disorders associated with obesity. 2-3<\/sup><\/p>\n

Several main components of ginger (particularly 6-gingerol and 6-shogaol) have been studied in vivo and shown to reduce fat accumulation, body weight, serum triglyceride levels, and improve insulin\/glucose tolerance in animal models of obesity. Reported mechanisms include inhibition of adipogenesis, regulation of lipid-metabolic gene expression, modulation of pro-inflammatory adipokine cytokines, activation of the Adenosine Monophosphate Activated Protein Kinase (AMPK) pathway, and changes in gut microbiota composition that contribute to metabolic improvements.4<\/sup><\/p>\n

Modern phytochemical analysis using techniques such as Liquid Chromatography\u2013Mass Spectrometry allows the identification of bioactive compounds in red ginger extract, including gallic acid, naringenin, kaempferol, catechin, quercetin, rutin, and various gingerolsand shogaols, which collectively may exert synergistic effects on metabolic parameters (glucose, triglycerides, free fatty acids) through antioxidant, anti-inflammatory, and enzyme\/lipid metabolism regulation mechanisms. Therefore, studies combining LC-MS profiles and metabolic parameter measurements in animal models of obesity are relevant to link the chemical components of the extract with the observed therapeutic effects.2<\/sup><\/p>\n

Accordingly, this study was designed on the premise that the bioactive constituents of red ginger extr\/act (such as 6-gingerol, 6-shogaol, flavonoids, and phenolics) may contribute to weight reduction and improvements in glucose and lipid parameters (triglycerides and free fatty acids) in obesity-induced rats, with LC-MS employed to link the identified compounds to their observable pharmacological activities.2<\/sup><\/p>\n

Therefore, the present study seeks to assess the potential of bioactive compounds in red ginger extract to lower these parameters and explore its role as a natural therapeutic option for managing obesity and associated metabolic disorders.<\/p>\n

Materials and Methods\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <\/strong><\/p>\n

Materials<\/strong><\/p>\n

Red ginger rhizome samples\u00a0 collected from the Batubulan area, Gianyar, Bali, distilled water, 96% methanol, twenty-four Wistar rats,\u00a0 high-fat intake (60% standard diet, 20% duck egg yolk, 20% lard), standard feed (CP550), Meyer’s reagent, NaOH, oxalic acid solids, magnesium powder, sulfuric acid, anhydrous acetic acid, FeCl3<\/sub>, concentrated HCl, dilute HCl, chloroform, PP indicator, Folin-Ciocelteau, distilled water.<\/p>\n

Equipment<\/strong><\/p>\n

Erlenmeyer flasks, volumetric pipettes, evaporating cups, beakers, LC-MS (Shimadzu 8040), blender, rotary vacuum evaporator (Buchi type R 215), micropipettes, analytical balance, glucometer and test strip set, burette, clamps and stand, mouse cages, mouse drinking bottles, probes, and chemistry analyzer (ERBA-XL 100).\u00a0<\/strong><\/p>\n

Methods<\/strong><\/p>\n

Sample Preparation<\/strong><\/p>\n

Red ginger rhizomes were prepared by cleaning the samples in running water and then draining them. The samples were cut into smaller pieces and air-dried. Next, the samples were blended until smooth and weighed on an analytical balance, then the water content was calculated.<\/p>\n

Red Ginger\u00a0 Extraction <\/strong><\/p>\n

Red ginger powder (500 g) was macerated in 96% technical methanol at a ratio of 1:5 for 24 hours. The maceration was repeated three times for 24 hours. The extract was then filtered through filter paper to separate the filtrate from the pulp. A concentrated extract of red ginger rhizome was prepared by evaporating the solvent with a rotary vacuum evaporator.3,10<\/sup><\/p>\n

Phytochemical Testing<\/strong><\/p>\n

The flavonoid test on red ginger rhizome extract was performed by adding concentrated HCl and Mg powder to the extract. The flavonoid test was considered positive if the solution changed color to orange.<\/p>\n

The saponin test was performed by adding methanol extract of red ginger rhizome in a test tube with distilled water in a 1:1 ratio, then shaking the mixture vigorously for one minute until foam formed. A positive result for saponins was indicated by the presence of foam that persisted for several minutes.<\/p>\n

The alkaloid test on ginger rhizome extract was performed by adding Mayer’s reagent or dipotassium tetraiodomercurate to 1 ml of red ginger rhizome extract. The presence of alkaloids was confirmed by the appearance of a white precipitate.<\/p>\n

The steroid and triterpenoid tests were performed by reacting the extract with Liebermann-Bouchard reagent, anhydrous acetic acid and concentrated sulfuric acid (H2<\/sub>SO4<\/sub>). \u00a0\u00a0\u00a0The steroid test was considered positive if the extract changed color to blue-green. The triterpenoid test was considered positive if the extract changed color to red-purple.<\/p>\n

The phenol test can be performed by adding Folin-Ciocalteau reagent to red ginger rhizome extract and then adding Na2<\/sub>CO3<\/sub> powder to create an alkaline environment. This test is considered positive if the extract turns blue.<\/p>\n

The tannin test is performed by reacting 1% FeCl3<\/sub> with the sample. A positive tannin test is identified by observing the color change of the extract to blackish green.<\/p>\n

LC-MS Analysis of Red Ginger<\/strong><\/p>\n

The concentrated extract of red ginger rhizome was purified using Solid Phase Extraction (SPE). First, a Sep-Pak C18 column (1 cc, 100 mg) was conditioned with 1 ml of an 80:20 acetonitrile-water mixture, followed by 0.5 ml of protein precipitation solution. Next, the column was eluted with 0.5 ml of an acetonitrile-water mixture, followed by 0.25 ml of a 200 mM ammonium formate solution in a 50:50 acetonitrile-methanol mixture. The final eluate was then mixed with 0.2 ml of an acetonitrile buffer solution (25:75) containing 25 mM ammonium formate at pH 4.5. The resulting mixture was filtered through a 0.45 \u00b5m cellulose acetate filter membrane, degassed, and injected into the LC-MS instrument. The obtained data were processed using LC-MS, and the chromatograms were analyzed using MassLynx software version 4.<\/p>\n

Animal Treatment<\/strong><\/p>\n

With approval from the Animal Ethics Committee (No. B\/203\/UN14.2.9\/PT.01.04\/2024), twenty-four female Wistar rats were allocated into four groups and subjected to the following treatments:<\/p>\n

K1: Negative (Normal) control group<\/p>\n

K2: Positive (Obese) control group<\/p>\n

K3: Obese + red ginger extract at 100 mg\/kg bw<\/p>\n

K4: Obese + red ginger extract at 200 mg\/kg bw<\/p>\n

Eighteen female rats were given a high-fat diet, and six rats were fed a standard diet. Red ginger rhizome extract was administered after the rats were declared obese, as measured by a Lee index value > 0.3. Body weight was measured weekly for four weeks. After four weeks, the rats were fasted for 10 hours to collect blood samples. Blood samples were obtained from the orbital cavity of rats using a capillary tube and transferred into a 3 mL syringe, then left to clot for 30 minutes at room temperature. Serum was isolated by centrifugation at 1000 rpm for 10 minutes, after which it was collected and stored in microcentrifuge tubes. Determining Glucose Levels<\/p>\n

Blood glucose levels are measured using a glucometer. A blood sample is drawn, touched to the test strip on the glucometer, and then left to stand until the blood glucose reading is recorded. Normal fasting blood glucose levels in mice are 50-125 mg\/dl; if the reading is greater than 125 mg\/dl, the mouse is considered diabetic.11<\/sup><\/p>\n

Determining Triglyceride Levels<\/strong><\/p>\n

Serum triglyceride levels are measured using a chemistry analyzer, the ERBA XL-100 instrument. The reagents used to determine triglyceride levels are Sekisui Medical Triglyceride Kit reagents Lot No. R1: 105R10 and R2: 105R10.<\/p>\n

Triglyceride levels are determined using a control run, placing 260 \u00b5l of Reagent R1 and 130 \u00b5L of Reagent R2 in the instrument according to the order indicated on the reagent tray. A 3.0 \u00b5L control and sample were placed in the instrument and measured at a wavelength of 600-700 nm. Afterward, a sample run was performed by inserting 3.0 \u00b5l of sample into the instrument. The instrument was then run, with the sample absorbance measured at a wavelength of 546 nm.11<\/sup><\/p>\n

Analysis of Free Fatty Acid\u00a0 Content<\/strong><\/p>\n

Free fatty acid levels were measured by alkalimetric titration after extraction using the Folch method. Extraction was carried out by dissolving 200 \u00b5l (0.2 ml) of blood serum in 10 ml of a neutral solution of methanol and chloroform (1:2) v\/v. Water was then added to the mixture to achieve phase separation. The chloroform phase containing the lipids was separated from the other phase.<\/p>\n

Two to three drops of phenolphthalein indicator were added to the sample, and the blood serum was titrated with 0.01 N NaOH solution. The titration was stopped when the solution changed color to a faint pink. The volume of NaOH was recorded, and the free fatty acid content was calculated in mmol\/L.11<\/sup><\/p>\n

Data Analysis Using Statistics <\/strong><\/p>\n

Statistical analysis of the research data was performed using ANOVA in SPSS version 23.0 with a 95% confidence level. The procedure included several stages: data normality was first assessed using the Shapiro\u2013Wilk test (suitable for sample sizes <30), with p > 0.05 indicating normal distribution. Homogeneity of variance was then evaluated using Levene\u2019s test, where p > 0.05 signified uniform variance across groups. For datasets meeting both assumptions, a One-Way ANOVA was applied, followed by an LSD post hoc test to identify intergroup differences. When the assumptions were not met, Tamhane\u2019s post hoc test was employed instead.\u00a0<\/strong><\/p>\n

Results <\/strong><\/p>\n

Phytochemical Testing of Extract<\/strong><\/p>\n

Phytochemical screening outcomes of the concentrated red ginger rhizome extract are displayed in Table 1.\u00a0<\/strong><\/p>\n

Table 1: Outcomes of phytochemical test on red ginger rhizome extract<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
Metabolite<\/strong><\/td>\nParameter<\/strong><\/td>\nTest Result<\/strong><\/td>\n<\/tr>\n
Flavonoids<\/td>\nOrange color<\/td>\n+<\/td>\n<\/tr>\n
Saponins<\/td>\nConstant foam<\/td>\n+<\/td>\n<\/tr>\n
Steroids<\/td>\nDark green color<\/td>\n+<\/td>\n<\/tr>\n
Triterpenoids<\/td>\nBrown ring<\/td>\n+<\/td>\n<\/tr>\n
Alkaloids<\/td>\nYellow precipitate<\/td>\n+<\/td>\n<\/tr>\n
Phenolics<\/td>\nBlue color<\/td>\n+<\/td>\n<\/tr>\n
Tannins<\/td>\nBlackish green color<\/td>\n+<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Description: \u00a0+ = present\u00a0 \u00a0– = absent<\/p>\n

LC-MS Analysis of Red Ginger Rhizome Extract<\/strong><\/p>\n

Compound content analysis of red ginger rhizome extract using LC-MS was performed by analyzing its mass spectrum and comparing it to the mass spectrum in the Chemspider database. Table 2 lists the eleven compounds identified in the crude extract of red ginger rhizome, namely gallic acid, \u03b1-curcumin, \u03b1-zingiberene, naringenin, 6-shogaol, kaempferol, catechin, 6-gingerol, quercetin, 8-gingerol, and rutin.<\/p>\n\n\n\n
\"\"<\/td>\nTable 2: Compounds contained in red ginger rhizome extract<\/strong><\/p>\n

Click here to view Table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Animal Treatment<\/strong><\/p>\n

Twenty-four female Wistar rats were fattened using a high-fat intake, which involved feeding them high-fat feed until their body weight reached obesity (Lee index > 0.3). Red ginger rhizome extract administration was associated not only with changes in glucose, triglyceride, and free fatty acid levels but also with a progressive decrease in body weight across the weeks. Changes in the rats\u2019 body weight over the course of four weeks are displayed in Figure 1.<\/p>\n\n\n\n
\"\"<\/td>\nFigure 1: The body weight progression of\u00a0 rats was observed over a 4-week period<\/strong><\/p>\n

Click here to view Figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Figure 1 and Table 3 show that four weeks of treatment with red ginger rhizome extract at doses of 100 and 200 mg\/kg BW reduced the body weight of obese Wistar rats. Both doses produced comparable effects in lowering body weight, and notably, the extract\u2019s anti-obesity activity helped restore the rats\u2019 body weight toward the normal range.\u00a0<\/strong><\/p>\n

Table 3: The average weight changes in Wistar rats were monitored for 4 weeks<\/strong><\/p>\n\n\n\n\n\n\n\n\n
Group<\/strong><\/td>\nK1<\/sub><\/strong><\/td>\nK2<\/sub><\/strong><\/td>\nK3<\/sub><\/strong><\/td>\nK4<\/sub><\/strong><\/td>\n<\/tr>\n
Start (g)<\/strong><\/td>\n160.23 \u00b1 1.03b,c,d<\/sup><\/td>\n295.45 \u00b1 1.58a<\/sup><\/td>\n294.73 \u00b1 3.31a<\/sup><\/td>\n295.98 \u00b1 1.90a<\/sup><\/td>\n<\/tr>\n
Week -1(g)<\/strong><\/td>\n161.90 \u00b1 1.39b,c,d<\/sup><\/td>\n301.67 \u00b1 1.11a,c,d<\/sup><\/td>\n288.57 \u00b1 1.64a,b<\/sup><\/td>\n287.89 \u00b11.40a,b<\/sup><\/td>\n<\/tr>\n
Week-2(g)<\/strong><\/td>\n181.26 \u00b1 2.36b,c,d<\/sup><\/td>\n305.08 \u00b1 1.03a,c,d<\/sup><\/td>\n268.18 \u00b1 1.59a,b<\/sup><\/td>\n266.96 \u00b1 1.79a,b<\/sup><\/td>\n<\/tr>\n
Week -3 (g)<\/strong><\/td>\n192.24 \u00b1 1.94 b,c,d<\/sup><\/td>\n308.92 \u00b1 1.06 a,c,d<\/sup><\/td>\n247.41 \u00b1 1.48a,b<\/sup><\/td>\n246.36 \u00b1 1.30a,b<\/sup><\/td>\n<\/tr>\n
Week-4 (g)<\/strong><\/td>\n213.15 \u00b1 1.74 b,c,d<\/sup><\/td>\n312.35 \u00b1 1.00 a,c,d<\/sup><\/td>\n218.47 \u00b1 1.58a,b<\/sup><\/td>\n217.58 \u00b1 1.33a,b<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Description: Mean \u00b1 SD (n=6) is shown, with differing superscript letters in a row reflecting significant differences (p<0.05). a = negative\/normal control (K1), b = positive\/obese control (K2), c = red ginger extract 100 mg\/kgbw (K3), d = red ginger extract 200 mg\/kgbw (K4)<\/p>\n

Data Analysis from In vivo Test Results<\/strong><\/p>\n

At the end of the 4-week treatment period with red ginger extract, blood glucose, triglyceride, and free fatty acid levels were evaluated The data on blood glucose, triglyceride, and free fatty acid levels are illustrated in Figure 2 and Table 4.<\/p>\n\n\n\n
\"\"<\/td>\nFigure 2: Graph presenting the average measurements of\u00a0 glucose, TG, and FFA.<\/strong><\/p>\n

Click here to view Figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Table 4: Mean concentrations of glucose, TG, and FFA<\/strong><\/p>\n\n\n\n\n\n\n
Group<\/strong><\/td>\nK1<\/sub><\/strong><\/td>\nK2<\/sub><\/strong><\/td>\nK3<\/sub><\/strong><\/td>\nK4<\/sub><\/strong><\/td>\n<\/tr>\n
Glucose (<\/strong>mg\/dl)<\/strong><\/td>\n81.50 \u00b1 1.05b,c,d<\/sup><\/td>\n246.17 \u00b1 1.17a,c,d<\/sup><\/td>\n101,50 \u00b1 1.05a,b,d<\/sup><\/td>\n91.00 \u00b1 0.89a,b,c<\/sup><\/td>\n<\/tr>\n
Triglycerides (mg\/dl)<\/strong><\/td>\n60.00 \u00b1 1.79b,c,d<\/sup><\/td>\n325.67 \u00b1 1.63a,c,d<\/sup><\/td>\n122.50 \u00b1 1.05a,b,d<\/sup><\/td>\n112.50 \u00b1 1.05a,b,c<\/sup><\/td>\n<\/tr>\n
Free fatty acids (mmol\/L)<\/strong><\/td>\n8.53 \u00b1 0.46b,d<\/sup><\/td>\n11.96 \u00b1 0.99a,c,d<\/sup><\/td>\n9.08 \u00b1 0.69b,d<\/sup><\/td>\n6.79 \u00b1 0.52a,b,c<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Description: Mean \u00b1 SD (n=6) is shown, with differing superscript letters in a row reflecting significant differences (p<0.05). a = negative\/normal control (K1), b = positive\/obese control (K2), c = red ginger extract 100 mg\/kgbw (K3), d = red ginger extract 200 mg\/kgbw (K4).\u00a0<\/strong><\/p>\n

Discussion<\/strong><\/p>\n

Phytochemical Testing<\/strong><\/p>\n

The phytochemical profile of red ginger rhizome extract (Table 1) demonstrated the presence of several secondary metabolites, namely flavonoids, saponins, steroids, triterpenoids, alkaloids, phenolics, and tannins. Research by Sururi et al. (2022) reported that red ginger contains flavonoids, saponins, alkaloids, and triterpenoids, which have antioxidant activity.3<\/sup>\u00a0<\/strong><\/p>\n

LC-MS Analysis<\/strong><\/p>\n

As shown in Table 2, eleven compounds were detected in the crude extract of red ginger rhizome : gallic acid, \u03b1-curcumin, \u03b1-zingiberene, naringenin, 6-shogaol, kaempferol, catechin, 6-gingerol, quercetin, 8-gingerol, and rutin, which together may exert a synergistic effect against obesity and metabolic disorders.<\/p>\n

Gallic acid has been reported to protect pancreatic cells by improving \u03b2-cell function by inhibiting caspase-9-related cellular apoptosis.12<\/sup>\u00a0 Gallic acid can induce nuclear transcription, leading to differentiation and insulin sensitivity in adipocytes.13<\/sup>\u00a0 Kaempferol and 6-shogaol have also been found to protect pancreatic \u03b2-cells by preventing apoptosis in pancreatic \u03b2-cells and activating autophagy, which helps \u03b2-cell survival.14<\/sup> Rutin also plays a role in reducing carbohydrate absorption, facilitating glucose uptake in tissues, and inducing insulin secretion by \u03b2-cells.15<\/sup><\/p>\n

Furthermore, curcumin can act as an antidiabetic by reducing oxidative stress in diabetic patients, thereby reducing diabetes complications. Adab et al. (2019) reported that curcumin was effective in lowering excess body weight, triglyceride levels, and blood glucose.16<\/sup><\/p>\n

Another mechanism that influences these three parameters is by inhibiting enzymes in the body’s metabolism. The reduction in blood glucose levels is mediated through the inhibition of \u03b1-glucosidase and \u03b1-amylase enzymes. These enzymes function as key regulators in the pathways of carbohydrate metabolism and glucose production. The inhibition of these enzymes allows for controlled glucose production and protection against hyperglycemic states. Compounds that have this mechanism include catechin, quercetin, naringenin, and rutin.17<\/sup>\u00a0 The presence of free hydroxyl groups in catechin is closely associated with its effectiveness in inhibiting \u03b1-glucosidase.18<\/sup>Catechins further act to improve insulin resistance, suppress oxidative stress, regulate mitochondrial performance, and reduce glucose levels in the blood. \u00a0Furthermore, quercetin can activate the AMPK pathway and increase GLUT4 translocation, which plays a role in increasing glucose uptake in skeletal muscle cells. This increased glucose uptake in muscle cells can prevent insulin resistance.19<\/sup> Naringenin contributes to better glucose regulation through its effect on liver enzymes that govern gluconeogenesis and glycolysis.20<\/sup><\/p>\n

Unlike other compounds, 6-gingerol can activate the GLP-1-mediated insulin secretion pathway and regulate insulin granule exocytosis, thereby enhancing glucose-stimulated insulin secretion.21<\/sup> Furthermore, this compound can also increase glycogen synthase 1 activity, thereby increasing glycogen storage in skeletal muscle. \u00a08-gingerol, a structurally similar compound, has also been suggested to lower glucose, triglyceride, and free fatty acid levels because of its antioxidant capacity. Antioxidants play a crucial role in reducing the risk of diabetes complications due to their ability to combat oxidative stress. According to Lian et al. (2024), 8-gingerol significantly reduced the elevation of reactive oxygen species (ROS).22<\/sup><\/p>\n

Animal Treatment<\/strong><\/p>\n

According to Table 3 and Figure 1, administration of red ginger rhizome extract at 100 mg\/kg bw (K3) and 200 mg\/kg bw (K4) for 4 weeks significantly reduced the body weight of obese Wistar rats relative to the obese control group (p < 0.05). This outcome is attributed to the combined action of secondary metabolites with anti-obesity activity. Supporting evidence is provided by Bogoriani et al. (2025), who demonstrated that obese mice receiving lidah mertua leaf extract containing bioactive compounds also underwent significant weekly weight loss at the same dosage.24<\/sup><\/p>\n

Table 3 and Figure 1 further demonstrate that red ginger rhizome extract at 100 and 200 mg\/kg bw produced no significant difference, indicating that both doses were nearly equally effective in reducing the body weight of Wistar rats. This weight loss can occur due to decreased levels of triglycerides or fat in the body. Rampengan et al. (2024) reported that red ginger has anti-obesity properties containing rutin and curcumin compounds, which were obtained with the same compound content as this study.23<\/sup> The difference in compound content found in red ginger rhizome extract is caused by differences in the growing location of the red ginger plant and the solvent used in the extraction.<\/p>\n

In Vivo Data Analysis<\/strong><\/p>\n

Table 4 and Figure 2 demonstrate that oral administration of red ginger extract for four weeks at doses of 100 mg\/kg (K3) and 200 mg\/kg bw (K4) significantly (p < 0.05) in obese\u00a0 rats group. The positive control group exhibited marked elevations in glucose (246.17 mg\/dL), triglycerides (325.67 mg\/dL), and free fatty acids (11.96 mmol\/L), confirming obesity-related metabolic disturbances. In contrast, treatment with red ginger extract lowered glucose to 101.50 mg\/dL (K3) and 91.00 mg\/dL (K4), triglycerides to 122.50 mg\/dL (K3) and 112.50 mg\/dL (K4), and free fatty acids to 9.08 mmol\/L (K3) and 6.79 mmol\/L (K4).<\/p>\n

The reduction in these parameters indicates that the bioactive compounds in red ginger play a role in improving glucose and lipid metabolism. Gingerol and shogaol, the main components, are known to increase insulin sensitivity, inhibit lipogenesis, and enhance fatty acid oxidation. Furthermore, the anti-inflammatory properties of these compounds are thought to play a role in suppressing systemic inflammation that occurs in obesity.1-2,4-5<\/sup><\/p>\n

Figure 2 and Table 4 demonstrate that administration of red ginger rhizome extract for 4 weeks significantly (p < 0.05) lowered glucose, and profile lipid compared to the obese group. Glucose levels declined by 58.65% at 100 mg\/kg bw and 62.86% at 200 mg\/kg bw, compared to a 66.89% increase in the obese control group, confirming the antihyperglycemic potential of the extract. Similarly, triglyceride levels decreased by 62.39% and 65.46% at the respective doses, relative to an 81.58% elevation in obese controls, suggesting that lowering triglycerides contributes to body weight reduction. Free fatty acids were also reduced by 24.08% and 43.23% at 100 and 200 mg\/kg bw, respectively, whereas the obese control group showed a 28.69% increase. Notably, the 200 mg\/kg bw treatment exhibited superior efficacy in lowering free fatty acids compared to both the 100 mg\/kg bw dose and the normal control.\u00a0 Administration of red ginger extract for 4 weeks in obese Wistar rats demonstrated stronger effects on glucose and triglyceride reduction compared to lidah mertua leaf extract at equivalent doses and treatment duration, whereas its impact on free fatty acids was comparatively lower. For lidah mertua leaf extract, decreases at 100 mg\/kg bw were observed at 44.12% for glucose, 45.66% for triglycerides, and 53.36% for free fatty acids, while treatment at 200 mg\/kg bw reduced these parameters by 45.53%, 48.79%, and 63.82%, respectively.24<\/sup> These findings confirm that the bioactive compounds in red ginger extract play a crucial role in its activity. The novelty of this research lies in the identification of 11 bioactive compounds through LC-MS, which act synergistically and highlight the extract\u2019s potential as a phytotherapeutic candidate for managing metabolic disorders.<\/p>\n

The decrease in blood glucose levels in Wistar rats can occur due to the content of secondary metabolite compounds in red ginger rhizome extract which can help in inhibiting carbohydrate metabolism enzymes, namely \u03b1-glucosidase and \u03b1-amylase enzymes. This was reported by23<\/sup> Rampengan et al. (2024), where in their research, ethanol and hexane extracts of red ginger help in inhibiting metabolic enzymes, namely \u03b1-amylase and \u03b1-glucosidase. Compounds that potentially have this mechanism are ar-curcumin, rutin, 6-shogaol, catechin, and quercetin.18,19,25<\/sup> Other compounds such as gallic acid, naringenin, and 6-gingerol reduce blood glucose levels by increasing GLUT4 (glucose transporter 4),20<\/sup> while kaempferol can increase insulin sensitivity.14<\/sup><\/p>\n

Triglyceride levels can decrease due to inhibition of lipolysis, thereby lowering lipid levels in the body. This decrease in triglyceride levels also affects free fatty acid levels in the body, as triglycerides are the main building block for free fatty acid formation. This decrease in triglyceride levels in the body will cause weight loss in obese Wistar rats due to the reduction in stored fat. Free fatty acids are also reduced due to the influence of secondary metabolites that can reduce lipogenesis, thus preventing free fatty acid biosynthesis in the body.4<\/sup><\/p>\n

Red ginger contains 11 bioactive compounds identified through LC-MS analysis, namely gallic acid, ar-curcumin, \u03b1-Zingiberene, naringenin, 6-shogaol, kaempferol, catechin, 6-gingerol, quercetin, 8-gingerol, and rutin. These compounds have reported anti-obesity, hypoglycemic and hypolipidemic activities via AMPK activation, inhibition of adipogenesis, modulation of mitochondrial function\/thermogenesis (PGC-1\u03b1), pancreatic lipase inhibition and gut-microbiome effects.2,4-9,13-23, 25-2<\/sup>6<\/sup>\u00a0<\/strong><\/p>\n

Conclusion<\/strong><\/p>\n

Red ginger rhizome extract contains 11 bioactive compounds identified through LC-MS analysis, namely gallic acid, ar-curcumene, \u03b1-Zingiberene, naringenin, 6-shogaol, kaempferol, catechin, 6-gingerol, quercetin, 8-gingerol, and rutin, which collectively provide synergistic effects as phytotherapy candidates for the treatment of obesity and related metabolic disorders.\u00a0<\/strong><\/p>\n

Acknowlegement<\/strong><\/p>\n

The author would like to thank Udayana of University for granting the research work. Special appreciation is extended to the Department of Chemistry, Udayana University, for providing access to laboratory facilities. The author is also deeply grateful to Udayana University’s Flagship Research 2024 and the Institute for Research and Community Service (LPPM) of Udayana University for funding this study.<\/p>\n

Funding Source<\/strong><\/p>\n

The author(s) received financial support for the research, authorship, and\/or publication of this article through Udayana University’s 2024 Flagship Research Program, administered by the Institute for Research and Community Service (LPPM) Udayana University with\u00a0 research assignment agreement number : B\/255.320\/UN14.4.A\/PT.01.03\/2024.<\/p>\n

Conflict of Interest<\/strong><\/p>\n

The author(s) do not have any conflict of interest.\u00a0\u00a0\u00a0 <\/strong><\/p>\n

Data Availability Statement<\/strong><\/p>\n

This statement does not apply to this article<\/p>\n

Ethics Statement<\/strong><\/p>\n

This study involves an experiment on\u00a0 animals. Research using test animals has been approved by the Animal Ethics Committee of the Faculty of Veterinary Medicine, Udayana University with Animal Ethics approval (number; B\/203\/UN14.2.9\/PT.01.04\/2024).<\/p>\n

Informed Consent Statement<\/strong><\/p>\n

This study did not involve human participants, and therefore, informed consent was not required.<\/p>\n

Clinical Trial Registration <\/strong><\/p>\n

This research does not involve any clinical trials.<\/p>\n

Permission to Reproduce Material from Other Sources<\/strong><\/p>\n

Not Applicable<\/p>\n

Author Contributions<\/strong><\/p>\n