Development and Evaluation of Phytosomes Containing Callistemon citrinus Leaf Extract: A Preclinical Approach for the Treatment of Obesity in a Rodent Model

Abstract

Callistemon citrinus has several biological effects; it is anti-inflammatory, anti-obesogenic, antioxidant, hepatoprotection, and chemoprotective. Its bioactive compounds include terpenoids, phenolic acids, and flavonoids which have low oral bioavailability and absorption. This study aimed at developing phytosomes of C. citrinus to improve oral bioavailability and absorption. Phytosomes were formulated with soybean phosphatidylcholine and C. citrinus leaf extract using the thin layer sonication method. Phytosomes were evaluated by scanning electron microscopy (SEM), entrapment efficiency, solubility, and particle size determination. Antioxidant capacity and total phenolic, flavonoid, and terpenoid contents were also measured. The in vivo anti-obesogenic activity was evaluated. Phytosomes loaded with C. citrinus (P C.c) extract had small spherical shapes. The average particle size was 129.98 ± 18.30 nm, encapsulation efficiency 80.49 ± 0.07%, and solubility 90.00%; the stability study presented no significant changes in the average particle size at 20 °C. P C.c presented high antioxidant capacity. For the first time, ellagic acid is reported in this plant. The in vivo obesity study showed a strong anti-obesogenic activity of phytosomes with C. citrinus to reduce 40% body weight as well as morphometric and biochemical parameters.

Bioactive Compounds Formulated in Phytosomes Administered as Complementary Therapy for Metabolic Disorders

“…In addition, both products reduced excessive weight in the obese rats. The administration of C. citrinus phytosomes, even in low doses, further reduced the adiposity index and TG levels in obese rats, compared to the unformulated extract [200].…”

“…The group of Ortega-Pérez L.G. et al [200] prepared Callistemon citrinus leaf extract in phyto-phospholipid complexes aiming to use them (doses range 50-200 mg extract/kg) for weight gain prevention in Wistar rats fed with a hypercaloric diet. They obtained phytosomes with the C. citrinus extract of a small size, high entrapment efficiency, improved oral bioavailability and enhanced stability at 20 • C (over three months) [201,202].…”

“…Murraya koenigii extract on STZ-induced diabetic Wistar rats: ↓ serum glucose, urea, and creatinine [51] -Crategus aronia leaf extract on STZ-induced diabetic Wistar rats: ↓ serum glucose [50] -Citrullus colocynthis, Momordica balsamina, Momordica dioica extract on STZ-induced diabetic Wistar rats: ↓ serum glucose [176] -Chrysin on db/db mice: ↓ serum glucose, insulin, HOMA-IR, hepatic PEPCK; ↑ GLUT4 [179] -Rutin on STZ-induced diabetic Wistar rats: ↓ serum glucose, HbA1C, TC, TG, AST, ALT, MDA; ↑ HDL-C, SOD, GPx [182] -Curcumin on STZ-induced diabetic Wistar rats: ↓ serum glucose, TC, TG, LDL-C; ↑ HDL-C [185] -Berberine on db/db mice: ↓ serum glucose, TG [52] -Gymnema inodorum leaf extract on LPS-treated 3T3-L1 adipocytes: ↑ glucose uptake [26] -Tripterine (selenized) on high glucose-exposed podocytes: ↑ viability; ↓ NLRP3, apoptosis[191] Metabolic syndrome Callistemon citrinus leaf extract on obese Wistar rats: ↓ body weight, adiposity index, TG[200] -Soybean (Glycine max) on Wistar rats with high-fat diet: ↓ body weight, adipose tissue weight, food consumption, plasma TC, TG, LDL-C, VLDL-C[69] …”

Review on Callilstemon citrinus: Recent Approaches in Novel Drug Delivery System

“…C. citrinus phytosomes reduced biochemical and morphometrical features in wistar rat fed a heigh-fat diet, even at low dosages. In addition, the results demonstrated that boosting with Callistemon citrinus phytosomes reduced the animals' excessive weight 28 .…”

“…Every process was shielded from light. One method for increasing the bioavalibility and solubility of plant extract is the use of phytosomes [28] . In the emulsion, the C. citrinus phytosome average particle size of 129.98 nm±18.30 nm.…”