1 Introduction

The current century is dominated by chronic degenerative diseases compared to the last century of infectious diseases. Among the chronic diseases, diabetes mellitus is the prominent one with a higher morbidity rate and accounting for large mortality across the globe. The diseases in well-characterized with altered insulin sensitivity and increased glycemic load (Chen et al., 2017). The impaired glucose metabolism is often associated with higher glycemic load and subsequent activation of polyol pathway enzymes and thereby inducing glycemic stress (Luo et al., 2016). These oxidative damages induced to the different body parts leads to the development of secondary microvascular complications including nephropathy and retinopathy (Ginter and Simko, 2012). In the past few decades, there is an alarming increase in the diabetic population around the world and especially in developing countries including India (Saeedi et al., 2019; Lin et al., 2020). Recent epidemiological surveys indicated that over 150 million diabetic patients exist all over the world and which is projected to increase above 300 million by 2025 (Standl et al., 2019). Similarly, it has been proposed that the number of diabetic patients may be projected to be above 57 million by 2025 (Geldsetzer et al., 2018). Lack of early diagnosis and timely interventions may cause diabetic complications. Persistent hyperglycemia and hypertension are responsible for the development of microvascular complications like diabetic retinopathy, neuropathy and nephropathy (Ahmed et al., 2017). Thus the loss of life from premature death among persons with diabetes is greatest in developing countries.

Alternative systems of medicines provide valuable information’s regarding medicinal herbs useful in the management of diabetics and their complications (Shweta and Arunaksharan, 2017). Many such documented herbs have shown significant effects on lowering the elevated blood sugar level and in manage diabetic complications. In the present scenario, the clinically employed drugs are expensive and are not devoid of any secondary clinical complications during prolonged application (Gor et al., 2020). Hence research is being conducted to discover a new hypoglycemic drug with a high efficacy with minimal side effects. Though insulin is a highly useful tool in the management of diabetes/ hyperglycemia, it is also known to be associated with various risk factors such as local lipodystrophy at the injection site and weight gain after chronic treatment (Home and Itzhak, 2020).

This has led to the quest for novel anti-diabetic molecules that are having lesser secondary issues with respect to patient health. Anti-diabetic properties of plants have been well documented and many of them are used in Ayurveda (Butala et al., 2017). Several scientific pieces of research in herbals revealed that the medicinal herbs have potential hypoglycemic activities and can be a better alternative to their synthetic counterparts. It is therefore important to utilize the traditionally engaged herbal medicines in the pharmaceutical arena for the successful treatment of diabetes and associated secondary complications.

Mimosa pudica L. (Fabaceae) is a common plant with higher levels of phytochemicals including tannins, steroids, triterpenes and flavonoids glycosides, and other phenolic constituents (Parvathy et al., 2021). The root extracts of M. pudica was used against cobra bite by traditional users in the Villupuram district of Tamil Nadu (Vijay Kumar, 2021). The extracts of M. pudica are widely used in the treatment of headache, migraine, stomach-aches, as a sedative, to stop menstruation insomnia, diarrhoea, dysentery, fever, diabetic mellitus, piles and fistula (Majeed et al., 2021). It has also been reported that the extracts of M. pudica beneficially modulate stress, learning and memory in mice (Patro et al., 2016). In arginine induced acute pancreatitis the extracts of M. pudica has been found to be having ameliorative potentials (Kaur et al., 2016). The protective effect of the plant is also evident in other models such as heavy metal toxicity or organ toxicities (Onyije et al., 2018).

Besides these benefits, the plant is also reported to have hypoglycemic efficacy in multiple models. Tunna et al. (2015) has indicated the use of M. pudica in the management of glycemic stress associated with diabetes by the traditional communities of South Africa. Further, experimental evidence has indicated that the leaves of the plant are good hypoglycemic agents (Parasuraman et al., 2019). However, the tested extracts were predominantly alcoholic and therefore the efficacy can’t be corroborated to its traditional uses. Hence, we attempted to compare the efficacy of ethanol and aqueous extracts of the M. pudica against the glycemic insults induced by STZ in murine models.

2 Materials and methods

3 Results

3.1

3.1 Effectiveness on the different Mimosa pudica extracts on glycemic status

Intra-peritoneal administration of STZ caused a significant elevation in the basal (on day 0) random blood glucose level in comparison with non-STZ treated murines. Oral administration of ME and MA for 21 days causes a marked reduction in serum glucose levels compared to the STZ alone group. Reference standard metformin administration was also induced a significant diminution in the blood sugar levels. However, it was noteworthy that there were no significant changes between ME and MA treatment group with that of metformin treatment group (Fig. 1).

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Fig. 1

Changes in the initial fasting blood glucose levels and at the end of 21st day in the diabetic rats and the protective effect of Mimosa pudica ethanol (ME) and aqueous (MA) extracts.

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3.2

3.2 M. pudica extract treatment and changes in the fasting plasma insulin levels

Results indicated a marked and statistically significant reduction in the fasting insulin levels of diabetic rats compared to the normal animals (P < 0.001). However, pre-treatment with the MA and ME successfully improved the fasting plasma insulin levels along with the metformin (p < 0.05) (Fig. 2).

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Fig. 2

Changes in the levels of plasma insulin in streptozotocin induced diabetic rats and the protective effects of Mimosa pudica ethanol (ME) and aqueous (MA) extracts.

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3.6

3.6 M. pudica treatment and HbA1c levels in diabetic rats

The hemoglobin level was significantly decreased with an increase in the total glycosylated hemoglobin content in the STZ-induced diabetic rats. On contrary, treatment with ME and MA opposed the STZ-mediated Hb depletion and also in the elevation in glycosylated hemoglobin content over 21 days of ME/ MA administration (Fig. 3).

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Fig. 3

Changes in the haemoglobin and glycated haemoglobin levels of diabetic rats and the mitigating effect of Mimosa pudica ethanol (ME) and aqueous (MA).

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3.7

3.7 Changes in the levels of lipid peroxidation products in STZ-induced diabetic rats and the protective efficacy of M. pudica extracts

Lipid peroxidation was significantly increased (p < 0.001) in streptozotocin induced diabetic control group, thereby indicating oxidative degradation of lipids. Repeated administration of ME and MA significantly attenuated the oxidative stress response in diabetic rats, as noted by reduced lipid peroxidation level (p < 0.001) (Fig. 4). Further, in basal, hydrogen peroxide, ferrous sulphate induced lipid peroxidation, both ME and MA treatment for 21 consecutive days led to significant attenuation of oxidative stress. Metformin administration has shown marginal reduction in the lipid peroxidation in comparison with the STZ induced diabetic rats.

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Fig. 4

Changes in the lipid peroxidation status in the different treatment regimens including STZ control, protective effects of Mimosa pudica ethanol (ME) and aqueous (MA) extracts.

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4 Discussion

Diabetes and associated secondary complications have emerged as an important concern in the arena of health management (Hafner et al., 2014). Considering the association of diabetes with other diseases like cancers, cardiovascular risk, fatty liver incidences, and neural degenerative diseases, it is important to control the glycemic load and associated stress (Benil et al., 2017). Underlying factors for the development of type-2 diabetes mellitus include glycemic load and insulin resistance. Hence, the anti-diabetic drugs are more focused on insulin sensitization. However, the diabetic complications are often associated with the polyol pathway and subsequent oxidative stress cascades. Hence, the ability of an anti-diabetic drug to control the oxidative insults are therefore important factor in controlling the secondary diabetic complications (Narayanankutty et al., 2018).

Streptozotocin is widely utilized as the model for experimental induction of type 2 diabetes mellitus in rats (Parasuraman et al., 2019). Single dose of 60 mg/kg STZ has been shown to induce hyperglycemia in all the experimental animals. Further, the treatment with aqueous and ethanol extract of M. pudica have shown to reduce the glycemic status in these rats, subsequently increasing the insulin sensitivity. The phenolic compounds present in the M. pudica are also reported to have anti-diabetic properties in individual experiments. Besides, the plasma insulin levels is also improved in the M. pudica extract treated animals over the 21 days of treatment. It is possible that the bioactive phytoconstituents present in the plant might have improved the insulin production and sensitivity in these rats.

Diabetes mellitus is often associated with increased glycemic load that eventually induce the polyol pathway signaling and subsequent induction of glycemic stress in the body (Luo et al., 2016). The glycemic stress is reported to be characterized by the increased oxidative damages in the tissues, subsequently resulting the generation of large volume of reactive radical moieties (Sheela et al., 2017). These radicals cause significant damages to the lipid macromolecules of the cell membrane and also modulate various pro-inflammatory signaling cascades (Tang et al., 2010). Corroborating with the reports, the present study also observed increased lipid peroxidation in the diabetic control group and which may be an indirect indicative of the glycemic load persisting in these animals. Besides, these animals also had significantly reduced intracellular glutathione pool; in diabetic conditions, the enhanced polyol activation may diminish cellular NADPH pool and thereby reduce the glutathione reductases activity (Tang et al., 2010). Due to the diminished GR activity, the salvage pathway of glutathione synthesis gets inhibited and causing the diminution in cellular reduced glutathione pool. It is therefore possible that the reduction in GSH pool in chronic diabetic rats may also explain the alteration in the plasma insulin levels.

Further, the results indicated a strong protective effect in the different extract treated animals during the diabetic conditions. The cellular pool of reduced glutathione and subsequent reduction in the lipid peroxidation status and improved insulin production are also well-corroborated. It is thus possible that the antioxidant molecules present in the M. pudica might have increased the de novo glutathione production. The phenolic compounds are well-known inducers of the glutathione biosynthesis mediated through the Nrf2/ ARE pathway (Narayanankutty et al., 2019). Further, phenolic compounds present in various plants are also reported to enhance the activity of glutathione biosynthetic enzymes and are also present in the M. pudica (Job et al., 2021). Apart from these the treatment with M. pudica extract also improved the cellular vitamin levels (Vit. E and Vit. C); the vitamins are important in preventing the insulin resistance and associated oxidative insults to the patients (Mason et al., 2021). Hence, the improvement in the non-enzymatic antioxidants may be partially contributed to the improved insulin sensitivity and reduction in glycemic stress in these animals.

Besides, the activities of enzymatic antioxidant molecules including CAT, SOD, GST and GPx are also altered in the diabetic rats. These results are in concordance with the previous literatures indicating the diminished antioxidant enzyme activities in preclinical and clinical models (Kala et al., 2015). These enzymes are important scavengers of reactive molecules that are involved in the cellular detoxification machinery and redox balancing (Li et al., 2016). Hence, the present observation in the improved antioxidant enzymes activities in rats treated with M. pudica extract may also contributed to the antidiabetic and diabetic complication reducing properties.

Together with the altered antioxidant responses in diabetic rats, there observed a marked elevation in the liver function marker enzymes. Beyond that, the restoration of these hepatic marker enzyme activities to near-normal level by the M. pudica extracts may also indicate the protective function of the plant in diabetic model. Further, elevated activities of these transaminases are often reported to increase the diabetes-dependent ketogenesis in diabetic rats (Chen and Croxson, 2007). Hence, the reduction of hepatic transaminase activities may also indicate the possible reduction in secondary diabetic complications in these animals. The increased gluconeogenesis and ketogenesis observed in diabetes may be due to high level in activities of these transaminases. Hence, the transient reduction in the activity of these transaminases by M. pudica extracts may also responsible for the inhibition of diabetic complications in these rats.

Overall, the M. pudica extracts efficiently ameliorates the hyperglycemia and associated glycemic stress by re-establishing the cellular redox balance in these rats. Further, the possible role of M. pudica aqueous extract as antidiabetic compound may also supports its traditional uses as medicinal herbs.

5 Conclusion

The results are indicative of the potential of M. pudica extracts in preventing the glycemic load and associated oxidative damages in the rats. Further, the phytoconstituents in the extract also improved glutathione levels, possibly modulating GSH-biosynthesis. Hence, it is clear that the M. pudica can be a leading source of anti-diabetic drug candidate, which equally modulate the secondary diabetic complications.