Toxicity Profiling and Antihyperuricemic Activity of Goubion: A Polyherbal Formulation

The objective of the present study was to determine the acute and subacute toxicity profile of a polyherbal formulation called “Goubion” in addition to the in vivo antihyperuricemic study using fructose-induced hyperuricemia. Goubion is a combination of Colchicum autumnale (tuber), Tribulus terresteris (fruit), Vitex negundo (leaves), Smilax chinensis (root), Glycyrrhiza glabra (root), and Curcuma amada (rhizome). The acute toxicity study revealed no signs of mortality and morbidity at a single dose of 2000 mg/kg. Similarly, the results of the subacute repeated dose toxicity study exhibited no signs of mortality at any of the doses. However, significant changes in hematological, biochemical, and renal parameters were recorded at the dose of 60 mg/kg. Antihyperuricemic activity was tested at the dose of 15 mg/kg and 20 mg/kg of Goubion, respectively against 5 mg/kg Allopurinol. Based on the antihyperuricemic study, we infer that the Goubion has a significant hypouricemic action, as it remarkably decreased the elevated uric acid levels. The results also suggest the potential inhibitory capability of Goubion on xanthine oxidase dehydrogenase might be the mechanism behind the hypouricemic effect.


Introduction
Hyperuricemia is a clinical condition manifested by excess serum urate in the body. It is characterized by serum uric acid value greater than 6.8-7.0 mg/dL (404-416 μmol/L). Hyperuricemia is primarily manifested by either overproduction or underexcretion of urate. Increased production of urate is associated with increased cell turnover rates due to diseases, inherited defects in the purine metabolism, or increased synthesis of ATP. Underexcretion is generally due to decreased urate clearance, which could be a consequence of reduced secretion, accelerated reabsorption, or reduced fltration of urate [1]. Allopurinol and febuxostat are the most commonly used drugs for the management of hyperuricemia. Very few options are available owing to their availability and tolerability in addition to their efcacy. With the recent restriction on the use of febuxostat by the FDA, there is a paucity of options left, and that too associated with a number of adverse efects [2][3][4].
Use of medicinal plants in treating diseases has achieved immense attention in the past few years owing to their low toxic profle and cost. Moreover, low allergenicity is also an added advantage of employing plants in the management of various ailments. A number of plants have the potential to decrease serum uric acid. Flavanoids, coumarins, polyphenols, alkaloids, and iridoid glucosides signifcantly reduce elevated uric acid levels [5][6][7]. When individual medicinal plants are used, a desirable therapeutic efect is hard to achieve as compared to polyherbals. Te presence of diferent phytochemicals and compatibility with the different medicinal plants exert more efectiveness as compared to allopathic drugs with fewer side efects. Moreover, polyherbals, as compared to allopathic drugs, have a wider therapeutic window, with most of them being safe at high doses [8].
Te goubion is a polyherbal coded formulation intended to be benefcial in gout by reducing elevated serum uric acid. It is a combination of Colchicum autumnale (tuber), Tribulus terresteris (fruit), Vitex negundo (leaves), Smilax chinensis (root), Glycyrrhiza glabra (root), and Curcuma amada (rhizome). Tese plants and their combinations are used in traditional systems of medicine for the management of hyperuricemia. Autumn crocus, scientifcally referred to as Colchicum autumnale, belongs to the family Colchiaceae. In the past, it was included in the Liliaceae family [9]. A lot has been reported on the efectiveness of the plant in the management of gout. Te therapeutic efect is due to the presence of alkaloidal constituents such as colchicine [10]. Not just gout, the plant is also used in the management of familial Mediterranean fever (FMF), scleroderma, idiopathic recurrent pericarditis, Behcet disease, and secondary amyloidosis [11,12]. Tribulus terresteris, a fowering plant commonly known as puncture or yellow vine, belongs to the family Zygophyllacaea [13]. Te therapeutic activity of the plant is contributed by the rich composition of favanoids and steroidal saponin constituents. Te plant is commonly employed for the management of infammatory disorders, nephritis, and as a demulcent. Mishra et al. have also reported the antiarthritic activity of the fruits of the plant in rodents [14]. Vitex negundo belongs to the family Verbanaceae. Due to its richness in phytochemicals, it possesses various medicinal properties. Its therapeutic uses vary from antimicrobial, anti-infammatory, to anticancer [15]. Te plant has the property to stimulate urination and perspiration. Te plant is also mentioned in De Materia Medica as an analgesic, antiandrogenic, and anti-infammatory. Smilax chinensis, belonging to the family Liliaceae, is frequently employed traditionally for a number of ailments. It is used in the treatment of infammation, analgesia, and carcinoma [16]. Glycryrrhiza glabra, or licorice, belongs to the family Fabaceae [17]. It is employed for multiple indications. Traditionally, it is employed as an antiasthmatic, antitussive, anti-infammatory, and antiulcer drug [18]. Mango ginger, scientifcally referred to as Curcuma amada, is a member of the Zingiberaceae family. Te pharmacological actions of mango ginger are attributed to the abundant volatile oils in the plant rhizome [19]. Pharmacologically, it acts as an antibacterial, anti-infammatory, antithrombolytic, and antioxidant [20]. Various research studies have reported the antihyperuricemic activity of each of the ingredients of the polyherbal formulation [21][22][23][24].
Tough natural products are comparatively safe, sometimes adverse efects may happen after the consumption of these products [25,26]. It is therefore, utmost essential to evaluate the safety and toxicity of these formulations before their use in human. Te objective of the present study is to investigate the toxicity profle and in-vivo hyporuricemic potential of Goubion in rodents.  Table 1 were cleaned and weighed accurately. Te approximate amounts of the herb were mixed and boiled using 2 liters of distilled water for around 2 to 3 hours. Following fltration, the supernatant liquid was decompressed using a rotary evaporator and then subjected to lyophilization using a freeze dryer. Te lyophilized powder was given the name "Goubion."

Extraction. All the herbs listed in
Te formulated capsules were chemically and physically tested, and all the formulated capsules complied with all the pharmacopeial standards.

Identifcation of Biomarkers. Biomarkers in Goubion
have been identifed using Shimadzu UV-HPLC LC 20, which has a C-18 column. Water: acetonitrile was used as the mobile phase. A varying concentration of the mobile phase was used for the identifcation of gallic acid and protodioscin in Goubion. Gallic acid is the most commonly reported phenolic compound and is a hidden treasure of therapeutic activities [27]. It has been well documented that gallic acid is a signifcant constituent of the ingredients present in Goubion [28][29][30][31][32][33]. Due to the variety of ingredients in Goubion, it is a rich source of biomarkers. However, because of the availability of gallic acid and protodioscin standard, only these were identifed. 10 mg of the content of the Goubion capsule was used for the preparation of the sample solution in the mobile phase as solvent corresponding to 0.1 mg/ml.  [35] were used for the single dose oral acute toxicity. Prior to the initiation of the test, mice were fasted for 24 hours. Six animals, three females and three males, were administered a single dose of 2000 mg/kg of the prepared formulation. After dosing, each animal was observed individually for the frst half of an hour and repeatedly for the frst 24 hours, with special emphasis in the frst 4 hours and daily for a period of 3 days; thereafter, they were humanely sacrifced. Changes in mucous membranes and eyes, fur and skin, central nervous system efects (drowsiness, tremors, and convulsions), autonomic efects (piloerection, lacrimation, and salivation), water consumption, food consumption, and mortality were observed [36].

Subacute Toxicity Test.
Te OECD 427, 2008 guidelines and a similar study by Ishtiaq et al. [35] were used for the repeated-dose oral toxicity for 28 days. Forty Wistar rats, twenty females and twenty males, were divided into 4 groups of 10 animals each, with males and females in the ratio of 1 : 1. Prior to the commencement of the test, rats were fasted for 24 hours. Tree groups were administered the following doses of the prepared formulation based on the adult human dose, i.e., 1000 mg/day: 15, 30, and 60 mg/kg, respectively. However, the fourth group, i.e., the control group, received only water and normal food. Te animals were administered their respective doses daily for twenty-eight consecutive days. Te animals were observed for mortality and any changes in behavior and food and water consumption. Changes in their body weight were also observed weekly. On the 28 th day, animals were anaesthetized using chloroform. Cardiac puncture was used to collect the blood from the rats. Te blood was collected into EDTA tubes for hematological analysis and nonheparinized tubes for biochemical analysis. Hematological analysis was performed using the HUMA-COUNT 80TS by Human Diagnostic, Germany, while biochemical analysis was achieved using instrument HUMALYZER 3500 by Human Diagnostic, Germany. Once the blood was collected, the rats were dissected, and vital organs were preserved in formalin for histopathological examination [37].

Hyperuricemia Rat Model.
Te efcacy of the prepared formulation for reducing elevated uric acid levels was evaluated by a fructose-induced hyperuricemia rat model as reported by Wang et al. with slight modifcations [38]. Twenty-fve male rats were divided into fve groups. Group one was designated as control, while the remaining groups were administered 10 percent fructose in water to induce hyperuricemia. Group two was given only 10% fructose solution; group three was also given 10% fructose solution along with 15 mg/kg/day of the prepared formulation; group four was given 10% fructose solution along with 20 mg/kg/ day of the prepared formulation: and group fve was given 10% fructose solution along with 5 mg/kg of allopurinol [39].
Water was used as a vehicle for the drugs. Group one and two were also given 0.6 ml of water to nullify the efect of the Evidence-Based Complementary and Alternative Medicine vehicle. All the drugs were given orally once daily for a period of 6 weeks. Blood samples were collected at the end of the study. Serum uric acid levels of the rats were detected using a Human Diagnostic Uric Acid Kit.

Statistical Analysis.
All the results were analyzed using SPSS version 20.0. Repeated measures ANOVA and one way ANOVA were applied for the analysis of toxicity tests and the in vivo comparison of hypouricemic activity in rats.

Biomarker Identifcation.
Gallic acid biomarker was identifed at a wavelength of 273 nm and protodioscin at 210 nm. Te retention time of gallic acid in the Goubion was found to be 3.502 min (Figure 1(a)) which was similar to that of gallic acid standard (Figure 1(b)), i.e., 3.499 min using mobile phase in the ratio of 75 : 25 v/v. Biomarker protodioscin was identifed at a wavelength of 210 nm with a retention time of 9.501 min in the standard and 9.499 min in the Goubion sample solution. Water: acetonitrile was used in the ratio of 60 : 40 v/v for protodioscin identifcation (Figures 2(a) and 2(b)).

Acute Toxicity.
Te mice were carefully observed for any signs and symptoms of toxicity for the initial 30 minutes and repeatedly for the frst 24 hours, with special emphasis in the frst 4 hours and daily for a period of 3 days after dosing. No signs or symptoms of toxicity were observed at the dose of 2000 mg/kg. Tere were no signifcant alterations in clinical parameters such as central nervous system efects and autonomic efects, as shown in Table 2. Moreover, the mice did not exhibit any signs of morbidity and mortality. Te observations found in the acute toxicity study indicate that the lethal dose of Goubion is greater than 2000 mg/kg.

Subacute Toxicity.
Tree diferent doses were administered to the rats, namely, 15, 30, and 60 mg/kg, while the control group only received the vehicle. Te study duration was four weeks. Hematological parameters including white blood cells, hemoglobin, MCH, MCHC, MCV, red blood cells, hematocrit, platelets, biochemical parameters including cholesterol profle, uric acid, creatinine, urea, SGPT, SGOT, alkaline phosphatase, body weight, and gross pathology of organs were focused on for any abnormalities. Te individual gross behavior of animals was also noted.
No signifcant changes in the animal's gross behavior were observed during the study period. Moreover, no mortality was reported in any of the groups.

Hematological Parameters.
Te hematological evaluation of diferent doses of Goubion in female rats revealed signifcant results(p < 0.05) ( Table 3). Te WBC count was signifcantly elevated at the dose of 15 mg/kg/day, while a decrease in WBC count was observed at the dose of 30 mg/  Similar to the female rats, the male rats also showed signifcant results (p < 0.05) (Table 4). However, no signifcant diference was observed in any of the hematological parameters at the dose of 15 mg/kg/day compared to control.
Although, at the dose of 30 mg/kg/day, a signifcant increase in hemoglobin, RBC, and hematocrit was found in contrast to the control, the WBC and platelet count were signifcantly decreased. Te dose of 60 mg/kg/day showed a signifcant diference in WBC, MCH, MCHC, MCV, hemoglobin, and platelet count.

Renal Parameters.
Te test drug showed a signifcant efect (p < 0.05) on uric acid at a dose of 60 mg/kg/day in both genders. Te mean uric acid of female rats signifcantly increased, while it signifcantly decreased in male rats compared to that of the control, but both were in the normal range. No signifcant diference was observed at the doses of 15 and 30 mg/kg/day. For creatinine, a similar pattern was observed in female rats. Te mean serum creatinine was signifcantly elevated at the dose of 60 mg/kg/day, whereas no signifcant dose-related diference was found at the doses of 15 and 30 mg/kg/day, in comparison to the control. However, the raised creatinine value was in the normal range. Conversely, the male rats depicted a diferent behavior in the mean serum creatinine values. Tere was a signifcant decrease in serum creatinine at the dose of 15, 30, and 60 mg/kg/day with respect to control but remained in normal range. However, no noteworthy diference was observed in serum urea at diferent dose levels, i.e., 15, 30, and 60 mg/kg, in both genders compared with that of control. Te efect of diferent doses of Goubion on renal parameters in female and male rats has been summarized in Tables 5 and 6.

Cholesterol Profle.
Te cholesterol profle of female rats was found to be signifcantly varied (p < 0.05) as highlighted in Table 5. In comparison to the control, no signifcant change was found in the serum cholesterol levels at 15 and 30 mg/kg/day. However, at 60 mg of dose/kg/day, a noteworthy reduction was seen in the serum cholesterol levels compared to the control, but it did not deviate from the normal range. Overall, a decreasing pattern was observed in the mean serum values of HDL cholesterol in comparison to the control. At 15 and 30 mg of dose/kg/day, the decrease in HDL cholesterol was statically signifcant (p < 0.05) with a mean diference of 11.30 and 6.95 to that of control. Tere was no remarkable diference in the mean LDL cholesterol values at 15 mg of dose/kg and control, but a signifcantly raised value was found at 30 mg/kg, while at 60 mg of dose/ kg, a remarkable decrease was observed. No noteworthy diference was observed in the mean triglyceride values at doses of 15 and 30 mg/kg, however, posthoc analysis revealed that the mean triglycerides value was signifcantly reduced at 60 mg of dose/kg to the mean triglyceride value of the control with a p value of 0.039.
Similar to the female rats, the male rats also exhibited remarkable diference (p < 0.05) in cholesterol profles, as shown in Table 6. Te mean serum cholesterol value of the control signifcantly varied from the mean serum cholesterol values at 30 and 60 mg of dose/kg, where a slight decreasing pattern in the mean values was observed. Te HDL cholesterol decreased at the diferent doses of Goubion; however, the mean HDL cholesterol at 15 mg/kg/dose signifcantly varied from that of control with a p value of 0.008. No remarkable diference was observed in the mean LDL cholesterol values between control and diferent doses of Goubion, though an increasing trend with respect to the increase in dose was observed. Decrease in the mean triglycerides value was found to that of control with signifcant reduction at the dose of 30 mg/kg.

Hepatic Profle.
Te hepatic profle of female treated rats revealed that no signifcant change (p > 0.05) was found in SGOT levels at 15 and 30 mg of dose/kg compared to that of control. On the contrary, the SGOT levels were signifcantly elevated (p < 0.05) in comparison to control. Tere was Results are expressed as mean ± SEM (n � 5). 2 One way ANOVA with posthoc Tukey was applied. 3 * indicates p < 0.05. Results are expressed as mean ± SEM (n � 5). 2 One way ANOVA with post-hoc Tukey was applied. 3 * indicates p < 0.05. 6 Evidence-Based Complementary and Alternative Medicine   (Table 5).

Evidence-Based Complementary and Alternative Medicine
In contrast to females, there was no signifcant change in SGOT levels in males at diferent test doses in comparison to control. Alternatively, with respect to control, the SGPT levels in male-treated rats signifcantly increased (p < 0.05) with a maximum dose of 30 mg/kg. No statistically significant variation was found in ALP levels compared to that of control (Tables 5 and 6).

Body Weight.
Variations in body weight were noted in female and male rats. A slight decrease was found in the weight of female rats at the doses of 30 and 60 mg/kg/day, while a gradual increase was found at 15 mg of dose/kg, as shown in Figure 3(a). Initially, the mean body weight of the control female rats was 200 g, and their fnal mean body weight was 199 ± 5.47 g. Te fnal mean body weights of the group treated at 15, 30, and 60 mg/kg were 206 ± 19.17 g, 196 ± 1.47 g, and 185 g, respectively, as compared to their initial body weight, which was 200 g.
In contrast to female rats, there was no statistical signifcant diference in the net efect in male-treated rats (p > 0.05) in the mean body weights at the end of the study with respect to their weights at the start of the study as illustrated in Figure 3(b). Te initial mean body weight of control male rats was 248 ± 1.22 g, and the fnal mean body weight was 256 ± 3.31 g. Te fnal mean body weights of the treated male rats at 15, 30, and 60 mg of dose/kg were 254 ± 2.44 g, 269 ± 2.44 g, and 253 ± 1.22 g, compared to their initial weights of 264 ± 2.44 g, 272 ± 1.22 g, and 250 g, respectively.

Effect on Histopathological Sections
6.1. Kidney. Te sections of the kidney of control female and male rats showed numerous glomeruli along with the tubules normal in appearance. Te histological examination of female and male rats treated with 15 mg/kg/dose of Goubion revealed preserved renal architecture similar to the control group. No signifcant pathology was seen. Similar to rats treated at 15 mg/kg, female and male rats treated with 30 mg/ kg of Goubion showed similar cellular symmetry to that of the control group, but at the dose of 60 mg/kg, marked congestion and infltration with atrophy of the glomeruli visible. Symmetry of cells was also disturbed (Figures 4(a)-4(h)).

Liver.
Te histopathological sections of the control female and male rat livers revealed normal hepatocytes and intact central and portal veins, alongside the hepatic artery, sinusoids, and bile duct. Female and male rats treated with 15 mg/kg of Goubion showed preserved hepatic architecture compared to that of control. In contrast, a female rat treated with 30 mg/kg of Goubion showed mild infltration along with the bile duct and radicles of the hepatic artery.
However, a liver section of the male rat illustrated no signifcant pathological changes in comparison to control. A liver section of the female and male rats treated with 60 mg/ kg of Goubion revealed signifcant pathological changes accompanied by moderate infammation and congestion (Figures 5(a)-5(h)).

Heart.
Te histopathological section of the hearts of female and male control rats revealed myocardium composed of cardiac muscle fbres which were long and cylindrical. Te heart sections of female and male rats treated with 15 mg/kg and 30 mg/kg of Goubion showed similar architecture to that of control. Te female and male rats treated with the highest dose of Goubion, i.e., 60 mg/kg revealed mild parenchymal hemorrhage and blood vessels that were dilated and congested (Figures 6(a)-6(h)).

Hyperuricemia Rat Model.
Te hypouricemic efect of Goubion in the hyperuricemic rat model is summarized in Table 7. Serum uric acid in rats treated with 10% fructose signifcantly (p < 0.05) increased in comparison to control. Goubion at a dose of 15 mg/kg/day and 20 mg/kg/day signifcantly lowered serum uric acid (p < 0.05) compared with the rats treated with 10% fructose. Similar to Goubion, 5 mg/ kg/dose of allopurinol also signifcantly reduced the serum uric acid.
When compared to control, Goubion at the dose of 15 and 20 mg/kg, remarkably reduced serum uric acid with a p value <0.05. In contrast, there was no noteworthy diference between rats treated with 5 mg/kg of allopurinol and control (p � 0.756).
Moreover, posthoc analysis also revealed that there was no signifcant diference in the serum uric acid in rats treated with 15 and 20 mg/kg of Goubion and 5 mg/kg of allopurinol 5 mg/kg.

Discussion
A number of plants possess signifcant activity in the management of hyperuricemia and infammation. Tey could serve as potential substitute candidates in comparison to conventional medicines, with maximum efcacy and minimal harm to the patient. Plants rich in polyphenols, alkaloids, coumarins, and favanoids may serve as potential candidates [40]. However, there is a dire need to evaluate their safety and toxicity profles before their use in humans for therapeutic purposes.
Te safe, efective dose to be used in humans is determined by an acute toxicity study. Acute toxicity testing is performed in rodent species for the determination of the potential toxicity of a newly developed product or chemical. Acute toxicity tests are carried out to determine the shortterm unwanted efects when a single dose of a drug is administered. It provides an estimate for the acute doses that are safe in humans and information regarding target organs of toxicity [41]. Mice are the most preferred rodent species for acute toxicity testing [42]. Goubion, when tested for acute toxicity in mice at a single dose of 2000 mg/kg, revealed Evidence-Based Complementary and Alternative Medicine no signs of mortality and morbidity. Goubion was found to be nontoxic and therefore has a lethal dose (LD50) greater than 2000 mg/kg [43].
Toxicity due to repeated dosing of a drug for a period of 28 days is referred to as subacute toxicity. Te accumulation potential of the new product or chemical is identifed during this study, along with the efect on target organs [44]. Tests for subacute toxicity are carried out to determine the toxicity index of the drug after repeated administration. Tese tests are helpful in choosing the diferent doses to be used in  Evidence-Based Complementary and Alternative Medicine subsequent studies for chronic toxicity. In addition, they also provide evidence for the support of initial clinical trials where the duration of treatment is up to four weeks [41,44].
Rats of both genders were treated with diferent doses of Goubion based on their body weight, namely, 15, 30, and 60 mg/kg. Te rats were evaluated for their hematological,   , and 185 g, respectively, as compared to their initial body weight, which was 200 g. Te variation in body weights suggests no compound related adverse efects on the body weight of the rats. Moreover, the decrease in body weight was of no toxicological signifcance, i.e., less than 10% of the mean control value [45].
No mortality at any of the doses was produced during the study period. Goubion was found to be nontoxic at repeated doses of 15 and 30 mg/kg. However, the dose was four times greater than the human dose, i.e., 60 mg/kg, mild changes were observed in the hematological, biochemical, and histopathological parameters. Despite variability in hematological parameters at diferent doses, all the hematological values were found to be in the normal range for rats [46]. Biochemical parameters, including serum marker enzymes, are of diagnostic signifcance in everyday clinical evaluation [47,48]. SGOT and SGPT are signifcant hepatic markers to assess drug-induced liver damage or any other type of hepatotoxicity. Te increase in liver enzymes at a dose of 60 mg/kg may be suggestive of hepatic tissue damage and impaired functioning of hepatocytes, as evident from the histopathology [49][50][51]. Similarly, kidney function parameters, i.e., creatinine and urea, were signifcantly raised when tested at 60 mg/kg. Tis is suggestive of the impaired renal  Results are expressed as mean ± SEM (n � 5). 2 One way ANOVA with posthoc Tukey was applied. 3 * p < 0.05 versus control group. 4# p < 0.05 versus fructose group. 5"a" indicates Goubion 15 mg/kg, "b" indicates Goubion 20 mg/kg.

12
Evidence-Based Complementary and Alternative Medicine fltration mechanism leading to kidney damage [52]. However, male rats did not exhibit an increase in creatinine at 60 mg/kg. Te exact mechanism of fructose-induced hyperuricemia is not yet known. However, it is suggested that fructose signifcantly elevates serum acid by augmenting the activity of xanthine oxidase dehydrogenase [23]. A fructose-induced hyperuricemic model was employed to explore the hypouricemic potential of Goubion in comparison to 5 mg/kg of allopurinol in rats' species. Goubion was tested at doses of 15 and 20 mg/kg. Serum uric acid was assayed in fructoseinduced hyperuricemic rats. Te results revealed that Goubion signifcantly reversed fructose-induced hyperuricemia. On the basis of the suggested mechanism of fructoseinduced hyperuricemia, it can be recommended that the potential mechanism behind the hypouricemic efect of Goubion could be its inhibitory action on xanthine oxidase dehydrogenase. However, further studies are required to confrm this mechanism of action.
Te plants used in the present investigation are a rich source of polyphenols, alkaloids, coumarins, and favonoids and could have played an important role in the antihyperuricmeic activity described by Goubion. Hyperuricemia strongly correlates with an increased risk of the development of gout and other cardiovascular and kidney diseases, etc. Te present study demonstrated that Goubion signifcantly reduces elevated serum uric acid levels and is safe to be used as a pharmacological drug.

Conclusion
Te results of the acute toxicity study revealed that the coded polyherbal formulation is nontoxic at a single dose of 2000 mg/kg. Te subacute repeated dose toxicity study exhibited no signs of mortality at any of the doses. However, signifcant changes in hematological, biochemical, and renal parameters were recorded at the dose of 60 mg/kg. In addition, the result of the antihyperuricemic activity revealed that the polyherbal drug composed of Colchicum autumnale (tuber), Tribulus terresteris (fruit), Vitex negundo (leaves), Smilax chinensis (root), Glycyrrhiza glabra (root), and Curcuma amada (rhizome) possessed signifcant hypouricemic activity in fructose-induced hyperuricemic rats. In the future, it is recommended to analyze the molecular-level hypouricemic mechanism of the formulation and further explore the hypouricemic potential.

Data Availability
Te data used to support the fndings of the study are available from the corresponding author upon request.

Conflicts of Interest
Te authors declare that they have no conficts of interest.