Utilizing bioassay- and TLC-guided column chromatography, fifteen secondary metabolites from Populus alba and eight compounds from Salix subserrata were isolated, including a novel plant metabolite salicyl ether and characterized using ultralviolet light (UV) absorbance, mass spectrometry (MS), ¹H-, ¹³C-NMR (nuclear magnetic resonance), heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC). The extracts, their sub-fractions and the isolated compounds exhibited promising antioxidant activities in vitro in DPPH and FRAP assays. Also, the extracts of P. alba leaf (PL), shoots (PS), and S. subserrata leaf (SL) demonstrated substantial antioxidant activities in vivo in the multicellular model organism Caenorhabditis elegans. For the first time, the isolated secondary metabolites, aromadendrin, tremuloidin, salicin, isorhamnetin-3-O-β-d-rutinoside, gallocatechin, triandrin, and chrysoeriol-7-O-glucuronide were investigated. They exhibited substantial antioxidant activities in vivo. Salicin, isorhamnetin-3-O-β-d-rutinoside and gallocatechin, in particular, protected the worms against a lethal dose of the pro-oxidant juglone (80 µM), decreased the endogenous reactive oxygen species (ROS) level to 45.34%, 47.31%, 68.09% and reduced juglone- induced hsp-16.2::GFP (green fluorescence protein) expression to 79.62%, 70.17%, 26.77%, respectively. However, only gallocatechin induced higher levels of sod-3 expression. These findings support the traditional use of Populus alba and Salix subserrata for treating inflammation especially when ROS are involved.

Nature is considered an indispensable source of natural products and natural products-derived drug leads. Over the last decade, the use of natural products-based medicine (herbal medicine or phytomedicine) has increased tremendously worldwide especially with the exceeding prevalence of metabolic disorders. Metabolic disorders are the major worldwide epidemic associated with obesity, diabetes mellitus, cardiovascular diseases associated with hyperlipidemia, and many other endocrine and nutrition-related issues. Since metabolic disorders are multi-factorial in their pathophysiology, they can be targeted by natural products that have synergy between diverse metabolites. Therefore, it is important to find the proper formulas not only for the treatment but also for reduction of associated risks and for prophylaxis and prevention of long-term complications. At the present work, a brief outline of the pathophysiology of metabolic disorders is provided. Additionally, natural productbased drug therapies that are currently applied in clinical trials attributed to metabolicrelated diseases are critically discussed.

Citrus fruits are among the most important economical crops, because of their nutritional value, medicinal importance, and unique flavor. Gas liquid chromatography-mass spectrometry of the hydro-distilled oil from the root resulted in the identification of 110 compounds with germacrene B (22%), aromadendrene (21.6%), α-santalene (7.1%), geijerene (4,81%), germacrene D (4.3%), and limonene (3.4%) as major constituents. In addition, chemical profiling the dichloromethane fraction of the root analyzed by high-performance liquid chromatography-photo diode array detector-electrospray tandem mass spectrometry afforded the identification of 43 compounds belonging to acridone alkaloids, coumarins, and flavonoids. Moreover, xanthyletin, citracridone I and II, clausarin, O-methylcitrusinine-I, and grandisinine were isolated as major metabolites using column chromatography and characterized depending on different spectroscopic techniques. Xanthyletin and citracridone I were investigated for their in vitro cytotoxicity against hepatocellular carcinoma and breast adenocarcinoma cell lines, and in vivo protective effect against cisplatin-induced nephrotoxicity and cardiotoxicity in different dose levels in a rat model. Xanthyletin and citracridone I showed protective activity against cisplatin-induced nephrotoxicity. It attenuated cisplatin-induced elevation of both serum urea and creatinine in a dose-dependent manner. Moreover, xanthyletin attenuated cisplatin-induced elevation of malondialdehyde and glutathione in both renal and cardiac tissues. Graphical abstract