Anti-obesity effect of argel (Solenostemma argel) on obese rats fed a high fat diet

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Abstract

Ethnopharmacological relevance

Solenostemma argel (Argel) is a desert plant commonly used in Egyptian and Sudanese traditional medicine to suppress appetite, for treatment of diabetes, and as an antispasmodic and anti-inflammatory agent. Previously the anti-diabetic, hypolipidemic and lipase inhibitory activities of Argel were reported in animal studies and in-vitro assays. However, its specific mechanism of action as an anti-obesity agent has not been studied before.

Aim of the study

Assessment of the possible anti-obesity effect of Solenostemma argel on diet-induced obesity and elucidation of its mechanism of action, as well as, standardization of the active plant extract.

Materials and methods

The ethanolic extract (EtOH-E) and its fractions (CH2Cl2-F: methylene chloride and BuOH-F: n-butanol) were prepared from the aerial parts of S. argel and studied at two dose levels; 200 and 400 mg kg−1 in a model of high fat diet (HFD) fed rats. The animals (72 Male Wister rats) were assigned into 9 groups: group (i) fed with normal diet and groups (ii-iv) fed with high fat diet (HFD) for 16 weeks and treated with orlistat, EtOH-E, CH2Cl2-F and BuOH-F in the beginning of the 8th week. At the end of the experiment, blood samples were analysed for lipid and liver biomarkers, glucose and insulin levels, as well as, adipokines and inflammatory markers. Liver and adipose tissues were examined histopathologically and their homogenates were used to determine levels of oxidative stress markers and lipogenesis-related genes. Body weight was monitored weekly during the experiment.

Results

Our data showed that consumption of S. argel significantly controlled weight gain, attenuated liver steatosis, improved the lipid profile, modulated adipokines activities, increased β-oxidation gene expression, as well as, decreased the expression of lipogenesis-related genes and ameliorated inflammatory and lipid peroxidation derangement. The ethanolic extract was also standardized using LC–MS analysis for its content of stemmoside C.

Conclusions

The current study revealed that S. argel is a promising Egyptian natural drug, rich in pregnane glycosides, and could be considered a new therapeutic candidate targeting obesity.

Introduction

Obesity is one of the most serious public health challenges of the 21st century (Alarcon-Aguilar et al., 2007), with more than 312 million clinically obese subjects worldwide (Kopelman, 2000). Fat deposition in adipose tissue and other internal organs is one of the characteristic features of obesity (World Health Organization, 2000; Ahima, 2006). Obesity could induce many chronic disorders such as type 2 diabetes, heart diseases, systemic hypertension, hyperlipidemia, arteriosclerosis, certain types of cancers and osteoarthritis (Alarcon-Aguilar et al., 2007). Obesity has also led to an increase in morbidity and mortality rates worldwide with high social and health costs. Therefore, great efforts have been devoted to discovering anti-obesity drugs worldwide (Hossain et al., 2007). Anti-obesity preparations of natural origin are appealing to consumers because of the general perception that if it is natural it must be more effective and safer than conventional treatments. In particular, many serious adverse effects were reported for synthetic drugs; sibutramine, orlistat and rimonabant, including gastrointestinal disturbances and significant side effects on the cardiovascular system (Padwal and Majumdar, 2007). Therefore, continuous search for new anti-obesity drugs from natural sources has become the current approach, due to their desirable pharmacological profiles and fewer side-effects (Chandrasekaran et al., 2012).

Solenostemma argel (Delile) Hayne is an Egyptian wild perennial dessert shrub, whose local Arabic name is ‘Argel’ (Harghel), and belongs to the family Asclepiadaceae (Plaza et al., 2005). It is distributed widely in Egypt, Sudan, Libya and Saudi Arabia (Hassan et al., 2001). The native Sudanese have commonly used the plant to suppress stomach pain and appetite (El- Kamali and Khaled, 1996; Mudawi et al., 2015; Shafek et al., 2012). Argel was also used traditionally as an anti-inflammatory, anti-rheumatic, antispasmodic agent and for the treatment of diabetes mellitus (Ibrahim et al., 2015; Innocenti et al., 2005; Khalid et al., 2012). The leaves were used as a remedy for neuralgia, sciatica and for the treatment of abdominal cramps, jaundice and cystitis (Ibrahim et al., 2015). Recently, the ethanolic extract of S. argel was proved to have a strong inhibitory activity against pancreatic lipase enzyme (Elbashir et al., 2018), in addition, it showed hypoglycemic (Deen and Al-naqeb, 2014) and hypolipidemic effects in rats (Osman et al., 2014). Previous chemical investigations in S. argel showed the presence of monoterpenes, pregnane glycosides, and acylated phenolic glycosides in the leaves (Kamel, 2003; Perrone et al., 2008, 2006).

Diet induced obesity animal model is considered one of the most popular and reliable models used in anti-obesity studies due to its similarity in modelling the common route of obesity in humans and related metabolic effects. It results in increased food intake, body weight gain, body fat accumulation, disruption in lipid profile, defects in anti-oxidant stability, and increased insulin resistance parameters (Buettner et al., 2007; Hariri and Thibault, 2010). The present work aimed to investigate the potential of the ethanolic extract (EtOH-E) of S. argel and its corresponding fractions in controlling weight gain associated with high fat (HF) feeding in rats and the possible underlying mechanisms. Due to the importance of the standardization of plant extracts for assessing the efficacy of herbal medicine, the EtOH-E of S. argel was standardized using LC-MS analysis for the isolated pregnane glycoside; stemmoside C.

Section snippets

Plant material

The aerial parts of Solenostemma argel (Delile) Hayne. was purchased at Haraz herbal store, Cairo, Egypt in 2016, and authenticated by Dr. Mohamed El-Gibali, Senior Botanist at El-Orman Botanic Garden. A voucher specimen was deposited in the Herbarium of Pharmacognosy Department, Faculty of Pharmacy, Cairo University (No. 2016-9-18).

Chemicals and reagents

Solvents used for plant extraction, fractionation and isolation were purchased from El-Gomhouria Co. (Cairo, Egypt) and were all analytical grade. For the

Effect on body weight (g), % weight gain, BMI and LI of rats fed with HFD

HFD fed animals exhibited a significant increase in body weight (101.63%) compared to the control group received a normal diet (393.96 ± 32.43 g vs. 195.38 ± 18.90 g; P ˂ 0.05). Treatment of rats with EtOH-E, CH2Cl2-F and BuOH-F significantly (P ˂ 0.05) suppressed the body weight gain by 11–27% after 4 weeks of treatment and this difference significantly increased (P ˂ 0.05) by 29–44% after 8 weeks of treatment (Table 1). The most significant suppression in body weight gain was achieved with

Discussion

Obesity and overweight are serious public health problems of high-risk factors. They are associated with several chronic disorders such as diabetes, heart diseases, hypertension, hyperlipidemia, arteriosclerosis, and osteoarthritis (Alarcon-Aguilar et al., 2007). Discovering new therapeutic agents for the management of obesity is a challenging goal. In continuation of our interest in natural medicines with anti-obesity effects, Solenostemma argel (Argel) was chosen for the current study. Argel

Conclusion

The alarming statistics on obesity unambiguously evidences that it should be considered a threat to the general health of the global population since it is associated with an increased risk for many serious diseases. In this study, we used an HFD-induced obesity rat model to verify the anti-obesity effects of S. argel. S. argel controlled weight gain, attenuated liver steatosis, improved lipid profile, decreased lipogenesis, modulated adipokines activities, increased β-oxidation gene expression

Conflicts of interest

None.

Authors contribution

Conceiving and Design of the experiment: E. A. Abdelsattar, D.A. Al-Mahdy, M.S. Hifnawy. Writing of the paper: R.A. El- El-shiekh, D.A. Al-Mahdy, E. A. Abdelsattar. Performing the chemical study: R.A. El- El-shiekh. Performing the pharmacological Study: S.M. Mouneir, R.A. El- El-shiekh.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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