Background: Fumaria 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. Methods: Bio-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. Results: In-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. Conclusions: Fumaria 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.

Objectives. Salvia fruticosa Mill. (S. fruticosa) is widely used in folk medicine. Accordingly, the present study was designed to evaluate the antioxidant and anti‐inflammatory activities of S. fruticosa, and to determine the phenolic constituents of its extracts. Methods. The antioxidant activity was determined using 2,2‐diphenylpicrylhydrazyl assay. Total phenolic contents were estimated using Folin‐Ciocalteu reagent, and high‐performance liquid chromatography was performed to identify phenolic constituents. To evaluate the anti‐inflammatory activity, carrageenan‐induced mouse paw edema was determined plethysmographically. Key Findings. Different plant extracts demonstrated strong radical scavenging activity, where the ethyl acetate extract had the highest value in the roots and the lowest in the aerial parts. This antioxidant activity was correlated to the total phenolic content of different extracts, where rutin and luteolin were the most abundant constituents. Interestingly, both the roots and aerial parts revealed a significant anti‐inflammatory activity comparable to diclofenac. Conclusions. This study is the first to demonstrate pharmacologic evidence of the potential anti‐inflammatory activity of S. fruticosa. This activity may partly be due to the radical scavenging effects of its polyphenolic contents. These findings warrant the popular use of the East Mediterranean sage and highlight the potential of its active constituents in the development of new anti‐inflammatory drugs.

Aims. To evaluate the effect of Punica granatum (Pg) rind extract and its spray dried biopolymeric dispersions with casein (F1) or chitosan (F2) against Diabetes mellitus (DM) and diabetic neuropathy (DN). Methods. We measured the acute (6 h) and subacute (8 days) effect of various doses of Pg, F1, and F2 and the active compounds on alloxan‐induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks). In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA) was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications.

The prevalence of Diabetes mellitus (DM) is escalating rapidly worldwide, and associated with micro- and macrovascular complications. Diabetic neuropathy (DN) is a common complication of DM, and has a few approved therapies with limited efficacy and several side-effects. Herbal medicine is used worldwide as an effective alternative-medicine. The present study aims to investigate the activities of Ferula hermonis Boiss. EtAc (Ferula) and Sambucus nigra L. aqueous (Elder) extracts, and their potential active isolates; for acute (6 h) and subchronic (8 days) glucose homeostasis, in vivo antioxidant potential and DN amelioration in alloxan-induced DM mice model. DM was induced experimentally by injection of freshly prepared alloxan every 48-h for three times at a dose of 180 mg/kg. Utilizing tail-flick, hot-plate latencies (accessing thermal hyperalgesia) and von Frey filaments test (accessing tactile allodynia), DN was evaluated for longer period of time (8 weeks). The most active isolates from Ferula was ferutinin, and Kaempferol from Elder utilizing bio-guided fractionation and RP-HPLC steeping methods. Compared to glibenclamide (GB) and tramadol (TRA), as positive controls, the highest doses of tested compounds exerted remarkable hypoglycemic and antinociceptive activities. The best acute hypoglycemic effect was observed with ferutinin (1.4 folds more effective than GB). Elder has shown the best subchronic hypoglycemic effect (2.6 folds more effective than GB) and the greatest efficacy against tactile allodynia following a single-administration, yet required repeated administration for improvement of thermal hyperalgesia. Without the use-limiting-side-effects of existing therapies, Ferula, Elder and their active isolates have shown significant results in ameliorating DM and long standing diabetes-induced complications.

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