Abstract
BackgroundFumaria officinalis (F. officinalis, FO) has been used in many inflammatory and painful-ailments. The main aim of this work is to perform an in-depth bio-guided phytochemical investigation of F. officinalis by identifying its main-active ingredients. Optimizing pharmacokinetics via niosomal-preparation will also be done to enhance their in vivo antineuropathic and anti-inflammatory potentials, and to explore their possible-mechanism of actions.MethodsBio-guided phytochemical-investigations including fractionation, isolation, chromatographic-standardization, and identification of the most active compound(s) were done. Optimized niosomal formulations of F. officinalis most active compound(s) were prepared and characterized. An in vivo biological-evaluation was done exploring acute, subchronic, and chronic alloxan-induced diabetes and diabetic-neuropathy, and carrageenan-induced acute inflammatory-pain and chronic-inflammatory edema.ResultsIn-vivo bio-guided fractionation and chromatographic phytochemical-analysis showed that the alkaloid-rich fraction (ARF) is the most-active fraction. ARF contained two major alkaloids; Stylopine 48.3%, and Sanguinarine 51.6%. In-vitro optimization, analytical, and in vivo biological-investigations showed that the optimized-niosome, Nio-2, was the most optimized niosomal formulation. Nio-2 had particle size 96.56 ± 1.87 nm and worked by improving the pharmacokinetic-properties of ARF developing adequate entrapment-efficiency, rapid-degradation, and acceptable stability in simulated GI conditions. FO, ARF, and Nio 2 were the most potent antidiabetic and anti-inflammatory compounds. The reduction of the pro-inflammatory tumor necrosis factor-alpha (TNF-alpha) and Interleukin 6 (IL-6), and elevation the anti-inflammatory factor IL-10 levels and amelioration of the in vivo oxidative-stress might be the main-mechanism responsible for their antinociceptive and anti-inflammatory activities.ConclusionsFumaria officinalis most-active fraction was identified as ARF. This study offers an efficient and novel practical oral formulation ameliorating various inflammatory conditions and diabetic complications especially neuropathic-pain.
Highlights
Fumaria officinalis (F. officinalis, FO) has been used in many inflammatory and painful-ailments
The Reversed phase (RP)-HPLC investigation utilizing standard steeping and calibration curves method has shown that alkaloidrich fraction (ARF) contains 2 major peaks: Stylopine (Sty, 48.3%), and (II) Sanguinarine (San, 51.6%) (Figs. 2 and 3)
Fractionation of ARF has been performed using flash chromatography and Sty and San were isolated and identified chromatographically. These findings were confirmed utilizing in-line fraction separator and positive Nano-ESI–MS/MS system (Mwt: Sty, 324.3 g/mol, and San, 333.09 g/mol). 1H and 13C NMR have confirmed that Sty and San are the most active compounds in ARF (Table 3)
Summary
Fumaria officinalis (F. officinalis, FO) has been used in many inflammatory and painful-ailments. Raafat and El‐Zahaby Chin Med (2020) 15:40 plant that grows in many Eastern-Mediterranean countries. It has been used in the Asian folk-medicine in many inflammatory and painful ailments like conjunctivitis and rheumatism [2,3,4,5]. The plant phytochemically comprises many secondary metabolites especially the isoquinoline alkaloids [7,8,9] These alkaloids are determined in literature by diverse techniques mainly reversed Phase-HPLC methods [8]. The folk use of F. officinalis (Fumaria officinalis) in various chronic ailments, made it of interest to explore its effect on other inflammatory and metabolic disorders and their complications
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