An elevated blood sugar level is a symptom of a group of metabolic disorders called diabetes mellitus. This may be the result of either insufficient insulin production by the pancreas (Type 1) or ineffective insulin utilisation by the body (Type 2).¹ The exact causes of Type 1 are still unknown, but it’s believed to involve the immune system attacking insulin-producing cells.² In contrast, factors like being overweight or having a family history increase the risk of Type 2.³ Common symptoms include increased hunger, urination and thirst. Uncontrolled, hyperglycemia can result in life-threatening consequences such as heart attacks, insulin resistance DM, strokes, blindness and amputations.⁴ long-term usage of insulin therapy might have adverse effects such as fatty liver, problems with eating and insulin resistance.⁵ Ayurvedic practitioners have long used the flowering plant C. roseus to treat Type 1 and Type 2 diabetes, along with other conditions. Its flowers, leaves and roots are known for their medicinal properties.⁶ It is essential to investigate the effectiveness of C. roseus in the management of Diabetes Mellitus (DM) and to examine the phyto-constituents that may contribute to the control of this condition. Various health disciplines should be informed about the potential efficacy of C. roseus in the regulation of DM. This review aims to analyze existing research on C. roseus to see if it can effectively lower blood sugar and manage diabetes-related complications.

The systematic review followed the quality standards outlined in the PRISMA guideline and the protocol was not recorded in the PROSPERO database.

The utilization and welfare of laboratory animals are subject to guidelines established by relevant ethics committees and these guidelines were adhered to in all research studies included in this analysis.

We conducted a comprehensive search in PubMed and SpringerLink, Google Scholer for relevant studies published in English from the databases’ inception from January 2001 to May 2024 (Table 1). We also examined reference lists of key reviews to identify additional articles. Our search terms included combinations of “Catharanthus roseus Antidiabetic Animal Study” and “Vinca rosea antidiabetic activity” This initial search yielded 192 articles. After removing duplicates and excluding studies in languages other than English or those not relevant to our topic based on their abstracts, in this article, the selection was reduced to 24 original research publications.

The evaluation of research articles and academic works was based on their impact, importance and relevance. In the situation of investigations related to the antidiabetic and antihyperglycemic effects of C. roseus and comprehensive scrutiny of appropriate publications was carried out without any text restrictions on keywords used in the search methodology. Research that investigated the effects of C. roseus extracts or constituents on diabetic animal models or pancreatic cells, including mice, rats, rabbits, or pancreatic cells, was incorporated in the review. Exclusion criteria includes, article that was not written in English, literature with technical error, literature that where not meaningful to our search. Figure 1, represents inclusion/exclusion of study.

Figure 1:
Schematic Diagram for Inclusion/Exclusion of Studies.

Diabetes was induced in the experimental groups using the method extracted from each study, when applicable. Additionally, to determine the mode or route of administration of C. roseus, the studies were reviewed. and to collect data on the animal samples utilized. This included details such as sample size, type, the specific form of diabetes mellitus induced, as well as the sex and age of the animals. If one or more sample characteristics were missing, the studies underwent a second screening. Should the necessary data still be absent after this second review, the missing sample characteristics were noted by the reviewer. Importantly, these studies were not excluded from the overall analysis. Characteristics of studies were summarized in Table 2.^7–19

A total of 192 publications were discovered, encompassing research conducted until May 2024. Among these, 24 publications were selected for inclusion as they specifically examined the antihyperglycemic and antidiabetic properties of C. roseus.

Use SYRCLE’s RoB tool to conduct animal experiments to assess risk of bias.²⁰ Figure 2 below provides an overview of areas contributing to bias in included studies. However, inadequate guidance is provided regarding lack of accommodation, blindness and blindness of assessment results for the majority of the population. Sections were found to be at low risk for sequential design, baseline characteristics, blinded allocation, incomplete outcome assessment, missing data, selective teaching and other inequities. Conclusion of SYRCLE’s bias risk presented in Table 3 and Figure 2.^21–23

Figure 2:
Conclusion of SYRCLE’s bias risk.

The research on the use of C. roseus in the treatment of diabetes has shown that it can be effective in tackling the complex issues that are associated with the disease, especially in both type 1 and Type 2 diabetes mellitus. The reviewed studies offer strong support for the C. roseus is ability to regulate the essential physiological processes that are involved in diabetes, such as enzymatic activities, lipid metabolism and oxidative stress.

C. roseus have antidiabetic effects in several ways that are interrelated in some way. Rasineni et al. (2017) showed that C. roseus has alpha-amylase inhibitory activity which prevents the conversion of starch to glucose and thus decrease the postprandial hyperglycemia. This enzymatic inhibition reduces the uptake of glucose from the gut and therefore it reduces hyperglycemia which is a major issue in diabetic patients.^7,24

Also, the antioxidant activity of C. roseus as pointed out by Rasineni et al. (2017) and Alkreathy et al. (2020) helps in the reduction of oxidative stress which is usually worsened in diabetes.^7,25 Oxidative stress results in the loss of the pancreatic β-cells that are responsible for the production of insulin. C. roseus reduces oxidative stress by quenching ROS and thus maintains the proper functioning of these cells and possibly enhancing insulin release.^26,27

C. roseus has been shown to inhibit alpha-amylase,²⁸ an enzyme responsible for breaking down starch into simple sugars. This inhibition can help reduce the absorption of glucose from the gut, thereby lowering blood glucose levels.²⁹

Another significant aspect of the antidiabetic effect of C. roseus is its capacity to modulate the secretion of insulin. Espejel-Nava et al. (2018) found that the phenolic compounds, especially chlorogenic acid and gallic acid, found in the C. roseus plant may help in improving the insulin secretion due to the increased sensitivity of the β-cells to glucose.

In addition, vindoline, vindolidine and other alkaloids described by Tiong et al. (2013) have been found to possess hypoglycemic effects, suggesting that they enhance the function of β-cells. The aqueous leaf extract showed significant effects in reducing blood glucose levels among all extracts tested.¹¹ Vindoline administration to rats led to increased insulin secretion upon glucose stimulation, further supporting its potential role in addressing β-cell dysfunction for more effective type 2 diabetes treatment.²⁸

C. roseus with Ursolic Acid as discussed by Alkreathy et al. (2020) has revealed that the two compounds have a synergistic effect on lowering blood glucose and lipid profiles. This combination not only improves the hypoglycemic effect, but also indicates a decrease in the doses, which will help to reduce the negative impact on the body.²⁵

C. roseus significantly enhances the distribution of insulin, glucagon and glucose transport genes (GLUT-2 and GLUT-4), restoring their mRNA levels to near normal. A decrease in these glucose transport gene levels leads to hyperglycemia due to reduced glucose uptake. By restoring these levels, C. roseus improves glucose uptake in the liver, aiding in the management of hyperglycemic conditions associated with type 2 diabetes.^10,30

C. roseus holds promise as a therapeutic agent for managing diabetes by improving enzymatic activities, reducing lipid peroxidation levels and normalizing oxidative stress markers while showcasing hypoglycemic properties across various animal models studied.³¹

The antihyperglycemic activity of C. roseus Linn. supports the therapeutic role of the plant in diabetes mellitus management. A number of experimental investigations have demonstrated a significant reduction of blood glucose levels in animals and even better results than standard treatment drug glibenclamide, proving the efficiency of C. roseus. This plant not only enhances insulin release from damaged beta cells on exposure to glucose but also stimulates the genes of GLUT-2 and GLUT-4. In addition, C. roseus has the ability to increase the activity of key glycolytic enzymes and decrease diabetes mediated damage in both blood and tissue. The presence of bioactive compounds including gallic acid, vindoline and chlorogenic acid supports the hypoglycemic effect of the plant. These findings suggest that C. roseus could be a potential source of an alternative treatment for diabetes and more research should be carried out to test the efficacy of the plant in human subjects. If these positive effects are further observed in humans, C. roseus can be a natural remedy for diabetes with an ability to reduce the risk of complications and enhance the therapeutic strategies.