Psychotria malayana Jack leaf extract could effectively treat diabetes with lower toxicity

In a recent study published in Pharmaceuticals Journal, researchers performed several analytic experiments on the optimized Psychotria malayana Jack (P. malayana) leaf extract (OE) to evaluate its anti-diabetic, anti-inflammatory, and antioxidant properties. 

Specifically, they evaluated its α-glucosidase inhibition (AGI) potential, inflammation inhibitory activity using the soybean lipoxygenase inhibitory (SLOXI) test, antioxidant activity using the Ferric Reducing Antioxidant Power (FRAP) and 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assays, its toxicity using a zebrafish embryo/larvae model (Danio rerio), and liquid and gas chromatography–mass spectrometry (LC-MS and GC-MS) to analyze the metabolites present in the OE.

Study: In Vitro Anti-Diabetic, Anti-Inflammatory, Antioxidant Activities and Toxicological Study of Optimized Psychotria malayana Jack Leaves Extract. Image Credit: PeopleImages.com - Yuri A/Shutterstock.comStudy: In Vitro Anti-Diabetic, Anti-Inflammatory, Antioxidant Activities and Toxicological Study of Optimized Psychotria malayana Jack Leaves Extract. Image Credit: PeopleImages.com - Yuri A/Shutterstock.com

Background

Locally known as “salung” in Malaysia, P. malayana grows in many parts of the Philippines, Indonesia, Malaysia, and Papua New Guinea and has been used as a remedy for wounds, skin infections, and other dermatological conditions for centuries.

However, it garnered the attention of scientists as a remedy for diabetes owing to its inhibitory activity towards α-glycosidase and slowing down glucose absorption.

In their previous study, researchers found that P. malayana methanolic and water extract exhibited noteworthy α-glucosidase inhibitory activity, with half maximal inhibitory concentration (IC50) values of 2.71 and 6.75 µg/mL, respectively.

Moreover, these extracts contained several active anti-diabetic metabolites, such as palmitic acid and 1,3,5-benzenetriol, to name a few. Furthermore, in an adult zebrafish model of type 1 diabetes, its aqueous leaf extract showed exceptional anti-diabetic efficacy.

In type 2 diabetes (T2D), the body’s insulin sensitivity diminishes, thereby inducing insulin resistance, which, in turn, triggers an inflammatory response. Heightened inflammation further exacerbates IR and vice-versa, i.e., these two phenomena show a reciprocal relationship.

Results

OE demonstrated an excellent AGI activity that effectively prevented the absorption of disaccharides found in complex carbohydrates in the diet. Its dual action against enhanced adipogenesis and obesity could lead to significant weight loss. 

The DPPH assay exclusively quantifies hydrophobic while the FRAP assay measures the activity of hydrophilic antioxidant compounds.

In the former assay, OE showed an IC50 of 13.08 µg/mL, while in the latter, it demonstrated the capability to react with a ferric tripyridyltriazine (Fe3+-TPTZ) complex and an IC50 of 95.44 mmol TE/mg DW.

It also showed a lethal concentration (LC50) value of 224.29 µg/mL. It is higher than the previously reported value of 37.50 µg/mL for the methanol extract of this plant, suggesting that OE is safer and a potent anti-diabetic agent.

The administration of various concentrations of OE manifested what can collectively be called developmental retardation in the exposed zebrafish embryos.

At OE concentrations equal to or exceeding 100 µg/mL, malformations in the embryo started to show as early as 24 hpf, and they showed hatching defects.

In larval zebrafish, several morphological defects were observed, such as small eyes and short body lengths. At OE concentrations higher than or equal to 150 µg/mL, the decrease in the embryos’ eye and yolk sizes occurred in a concentration-dependent manner.

Major compounds detected in OE by GC-MS were butanedioic acid (succinic acid), propanoic acid, palmitic acid, and D-(−)-tagatose. 

Several different studies have shown the potential of these compounds. For instance, Natrus et al. demonstrated that propanoic acid mitigates endoplasmic reticulum stress induced by diabetes in rats' hypothalamus.

Likewise, Hardy et al. showed that palmitic acid inhibited glucose uptake but not basal glucose uptake. Furthermore, Ensor et al. demonstrated that D-tagatose reduced glycated hemoglobin (HbA1c) levels among T2D patients. 

LC-MS detected other putative compounds in OE, such as isoaloeresin A, isorhamnetin, procyanidin B3, moracin M-3′-O-β-D-glucopyranoside, and leucopelargonidin.

Although there is a lack of evidence about the potential anti-diabetic, antioxidant, and anti-inflammatory capabilities of Isoaloeresin A is found in Aloe ferox, a plant known for its anti-inflammatory compounds.

Moracin M-3′-O-β-D-glucopyranoside has been shown to induce a hypoglycemic effect in rat models of T2D. In addition, it could help treat inflammatory illnesses. Procyanidin B3 has been shown to possess antioxidant properties and inhibit glucosidase.

Of all the compounds detected in OE, myo-inositol, isorhamnetin, and procyanidin B3 demonstrated all three bioactivities: anti-diabetic, anti-inflammatory, and antioxidant.

Conclusions

In this study, the researchers successfully increased the bioactivity and decreased the toxicity of the methanol extract of P. malayana leaf (OE).

Thus, they have even applied for a patent for its optimized extract as a trade secret (Reference number: TS 2023-01) at International Islamic University Malaysia.

Overall, compared to the prior state of the art, OE achieved higher inhibitory activity against α-glucosidase, higher efficacy in inhibiting soybean lipoxygenase-induced inflammation, and antioxidant properties while showing lesser toxicity. Most importantly, OE showed a higher therapeutic index, suggesting it is potent and safe for pharmaceutical use.

Additional research is necessary to isolate, identify, and quantify other bioactive compounds that may be present in OE.

Nonetheless, this discovery sets the stage for conducting in vivo and clinical trials on this compound.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

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