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Hyptis Jacq. (Lamiaceae) has been used in traditional medicine for the treatment of many diseases around the world. However, Harley and Pastore in 2012 proposed a new circumscription for this large genus, reducing its number of species, but supporting its monophyly. Hyptis and Peltodon were used as keywords, and triage of articles was performed using genus delimitation sensu Harley and Pastore. Only 29 species have some type of record in the literature for their medicinal use and chemical description, corresponding to 20% of the 148 species. Most cited biological activities were the antioxidant activity, reported for 9% of the species, and the antifungal activity reported for 5% of the species. For 11% of the species was described the essential oil composition, while non-volatile compounds were reported for only 6% of them. Terpenes, flavonoids, and caffeic acid derivatives are the most reported compounds for this genus. Only 8% of the species are reported as medicinal, with potential as antibacterial and antiparasitic, pointing to relevance of Hyptis to bioprospecting studies, especially in South America and Africa. However, there is a lack of studies regarding isolated compounds concerning their toxicology and efficacy, important information to achieve the production and the effective use of Hyptis as a herbal medicine.

Since the early days of medicine, chemical substances derived from animals, plants, and microorganisms have been used for treatment of various diseases. Among these, products derived from plants have dominated the pharmacopoeias for thousands of years, providing an inexhaustible source of medicinal resources. Croton L. is the second largest genus of Euphorbiaceae, comprising about 1300 species of trees, bushes, and herbs. Croton sphaerogynus Baill. belongs to the same clade of Croton cajucara Benth, used in traditional medicine. The aim of this study was to characterize the antioxidant activities of extracts and isolated flavonoids obtained from leaves of C. sphaerogynus. Chemical composition of leaf extracts and its fractions (flavonoid contents) and in vitro antioxidant properties were examined. Two flavonoids were isolated: quercetin 3-O-methyl ether and kaempferol 3-O-methyl ether. Antioxidant activity was higher, especially for fractions composed mainly by quercetin 3-O-methyl ether compared to crude extract and other fractions. For those fractions, EC 50 values were found to be close to the ones presented by quercetin when they were analyzed for their radical scavenging activities.

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Flavonoids and other phenolics are groups of natural bioactive compounds widely distributed in edible plants and are well documented to possess biological potential. Hyptis (Lamiaceae) is used in Brazilian folk medicine to treat various diseases. The aim of this study was to evaluate the antioxidant, anti-acetylcholinesterase, cytotoxic, antiviral and antibacterial potential of Hyptis radicans and Hyptis multibracteata by isolating and characterizing major constituents and their biological activities. H. radicans and H. multibracteata were dried, powdered and macerated in 70% ethanol which resulted in a crude ethanol extract (EE) for each species. EE were dissolved in 50% methanol and then was fractionated by partition with hexane and ethyl acetate; were obtained three phases: hexane phase (HP), ethyl acetate phase (EAP) and hydromethanol phase (HMP). EAP from H. radicans was the sample that presented the highest levels of total phenolic content, especially flavonoids, and was the sample with the high antioxidant activity with promising values of EC 50 : DPPH (32.12 µg mL-1), ABTS (5.04 µg mL-1), Metal chelator assay (42.36 µg mL-1), TBARS (40.46 µg mL-1) and nonsite-Specific Hydroxyl Radical-Mediated 2-Deoxy-D-ribose Degradation (NS-Spe) with EC 50 of 75.08 µg mL-1. EE from H. radicans showed high antioxidant activity for FRAP and ORAC with EC50 of 6.01 and 2.68 µg mL-1 , respectively and had the highest amount of rosmarinic acid (17.64 mg ρ-CE g-1). HMP from H. radicans showed high antioxidant activity in Site-Specific Hydroxyl Radical-Mediated 2-Deoxy-Dribose Degradation (S-Spe) assay with EC50 of 0.32 µg mL-1 and had the highest content of chlorogenic acid derivatives. Regarding the results of cytotoxicity, HP from H. multibracteata induced the death of more than 80% of RAW 264.7 Cell Lines at 100 µg mL-1. Nepetoidin B, isolated from H. multibracteata had the best EC 50 (52.73 µg mL-1) for antiacetylcholinesterase activity. Antibacterial activity was evaluated in vitro against two Gramnegative bacteria, Pseudomonas aeruginosa and Escherichia coli, and a Gram-positive Bacillus subtilis. Phases from H. multibracteata were more effective on inhibiting B. subtillis with MIC 50 of 23.6 μg mL-1 and 12.13 μg mL-1 for HP and EAP, respectively. HP was also activity against P. aeruginosa with MIC 50 of 37.55 µg mL-1. EE and HMP phase from H. radicans showed moderate anti-HIV-1 activity (MIC 50 159 µg mL-1 ; MIC 50 180 µg mL-1). Contents of total phenolic were not the main sample feature to define this activity, but there was correlation between Rosmarinic acid contents and anti-HIV1 activity of H. radicans. Cirsimaritin and litospermic acid A were isolated for the first time, being the first time that they are described for the genus Hyptis. This study provides the first evidence of chemical and biological potential for these two Brazilian native species of Hyptis.