An Insight into the Hepatoprotective Activity and Structure-activity Relationships of Flavonoids.

BACKGROUND: Flavonoids are a class of polyphenolic bioactive compounds obtained from plants, which have a wide range of chemical structures and properties. More than 9000 distinct flavonoid molecules have been identified and have been found to regulate numerous developmental processes and play key biological roles in living organisms. OBJECTIVE: This review aims to highlight the hepatoprotective potentiality of flavonoids and corelate their pharmacological activity with their chemical structure. METHODS: With the advancement in the field of research related to phytochemicals, it is evident that flavonoids have versatile health benefits, viz., antioxidant property, free radical scavenging capacity, anticancer activity. The basic structures are C6-C3-C6 rings with various substitution patterns, resulting in a succession of subclass compounds, and the relationships between chemical structures and bioactivity have previously been investigated. RESULTS: The hepatoprotective effects of bioactive flavonoids derived from plants have been widely linked to their antioxidant activity, antiinflammatory activity, effects on Sterol Regulatory Element- binding Proteins (SREBP), Peroxisome Proliferator-activated Receptor gamma (PPARγ) receptors, and inflammatory mediator cytokines according to numerous studies. The C2-C3 double bond at the A ring, as well as the hydroxyl groups of C3'or C4', and the carbonyl group at position C4, have been shown to augment their hepatoprotective activities; however, hydroxymethylation at C3' and C4' has been found to diminish the hepatoprotective activity. CONCLUSION: The impact of flavonoid moieties and the structure-activity relationship of flavonoids related to combating various hepatic disorders have been vividly discussed in this review paper.

Insight into the Various Approaches for the Enhancement of Bioavailability and Pharmacological Potency of Terpenoids: A Review.

Terpenoids are naturally occurring secondary metabolites that consist of isoprene units (i.e., 2-methyl-1,3-butadiene). Terpenoids became recognized because of their diverse pharmacological benefits, such as anti-cancer, anti-inflammatory, antioxidant, analgesic, antibacterial, antifungal, hepatoprotective, antiviral, and antiparasitic activities. But most of these compounds have limited lipophilicity, dissolution rate, aqueous solubility, and drug permeability, so they are not used effectively. The low bioavailability significantly interferes with the performance of terpenoids to cure diseases, and the absorption process of terpenoids also becomes disrupted; therefore, their bioavailability in the blood becomes insufficient to achieve optimal treatment activity. Thus, to overcome this limitation, some strategies are used, such as nanotechnology (nanoparticles, carrier complexation), cocrystal, and glycosylation. Thus, this review summarizes the chemistry of terpenoids, factors that limit the bioavailability of terpenoids, and strategies employed to date with their design principles and outcomes possibly increasing their bioactivity.

Synthesis, Structure Activity Relationship (SAR), and Biological Activities of Benzylideneacetophenones Derivatives.

BACKGROUND: Oxygen has double-edge properties as it is essential for life, but can also provoke oxidative stress by protein & lipid per oxidation. The persistent oxidative stress and excess LPO induce several inflammatory mediators such as prostaglandins and leuckotrienes by activating enzymes cyclooxygenase and lipoxygenase. The per oxidation can be blocked by free radical scavengers as antiinflammatory agents. Most of the anti-inflammatory agents, which inhibit the above mentioned enzymes, are associated with side effects such as ulceration and bleeding in gastrointestinal tract; so the attention is focused on benzylideneacetophenones having antinflammatory, antioxidant and gastric protectant activities by virtue of free radical scavengers. A systematic analysis of the structural features responsible for biological activities and a possible mode of their actions were proposed to be evaluated by synthesizing a set of compounds, screening them for anti-inflammatory, antioxidant and antiulcer activity. METHODS: The benzylideneacetophenones derivatives were synthesized employing the Claisen-Schmidt condensation. The structure of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory (carrageenan-induced rat paw edema assay), antioxidant (inhibition of lipid peroxidation) and antiulcer activity (indomethacin-induced gastric damage). Possible correlation between observed biological activities and substituents at different positions on rings was also studied. RESULTS: The data revealed that compounds 1e, 1m and 1l showed equivalent activity to indomethacin (reference drug) at the fourth hour at dose of 100 mg/kg. Among the tested compounds 1m & 1l exhibited the highest lipid per oxidation inhibitory activity (IC50 2.38µg/ml, 3.08 µg/ml) followed by 1i, 1h, 1e. In addition, all compounds at the tested dose level (100mg/kg, p.o.) exhibited varying degree of activity against ulceration induced by indomethacin. The compounds 1m, 1l, 1e, and 1i showed excellent activity (71-75%), whereas compounds 1d, 1h and 1j exhibited good to moderate (60-69%) activity. SAR analysis revealed that presence of electron donating groups on p- position of both rings A and B seems to enhance anti-inflammatory, antioxidant and antiulcer activity. CONCLUSION: The compound 1m (4-amino-4'-ethoxychalcone) and 1l (4-amino-4'-methoxychalcone) have equivalent antiinflammatory activity in comparison with the reference drug. Moreover, the same compounds also obtained promising antioxidant and antiulcer activities. Thus, I m could be explored further for development of potent anti inflammatory agent.