Antifungal and Antiproliferative Activity of Pistagremic Acid and Flavonoids Extracted from the Galls of Pistacia chinensis subsp. integerrima.

Pistacia chinensis subsp. integerrima (J.L. Stewart) Rech. f. is a plant known for its therapeutic applications in traditional medicine, which are related to its antimicrobial, anticancer, antioxidant, anti-inflammatory, analgesic, antidiarrheal, and muscle relaxant properties. The galls of P. chinensis are rich in triterpenes and flavonoids, and we here report the extraction of pistagremic acid (1), apigenin (2) and sakuranetin (3) from this source. The isolated compounds were tested against Aspergillus flavus, Candida albicans, Candida glabrata, Fusarium solani, Microsporum canis and Trichoderma longibrachiatum. The results highlighted the antimicrobial activity of flavonoids 2 and 3, suggesting that this class of molecules may be responsible for the effect related to the traditional use. On the other hand, when the compounds and the extract were tested for their antiproliferative activity on a panel of 4 human cancer cell lines, the triterpene pistagremic acid (1) showed a higher potential, thus demonstrating a different bioactivity profile. Structure-based docking and molecular dynamics simulations were used to help the interpretation of experimental results. Taken together, the here reported findings pave the way for the rationalization of the use of P. chinensis extracts, highlighting the contributions of the different components of galls to the observed bioactivity.

In Vitro α-Glycosidase Inhibition and In Silico Studies of Flavonoids Isolated from Pistacia integerrima Stew ex Brandis.

The galls of Pistacia integerrima are used in folk medicine for curing diabetes. The main aim of this study was the purification of flavonoids from galls of P. integerrima. The methanolic extract was subjected to column chromatographic analysis which afforded six flavonoids, namely, 3,5,7,4'-tetrahydroxy-flavanone (1), naringenin (2), 3,5,4'-trihydroxy,7-methoxy-flavanone (3), sakuranetin (4), spinacetin (5), and patuletin (6). These isolated compounds (1-6) were tested against α-glycosidase. The maximum antagonistic effect was noted against compound 6 (97.65%) followed by compound 5 (90.42%) and compound 1 (90.01%) at the same concentration (0.2 µg). The inhibitory potential of all tested compounds was significant with a degree of variation from each other. Docking studies showed that all studied compounds interact with the active site residues via hydrogen bond interactions with hydroxyl groups, and thus, inhibition was enhanced. Hence, this finding would be the first screening of isolated flavonoids for α-glycosidase activity and with the mechanism of action. These flavonoids should be further investigated as candidate drugs for combating diabetes mellitus.

Phytochemical Analysis and In Vitro and In Vivo Pharmacological Evaluation of Parthenium hysterophorus Linn.

The main aim of this research was to explore Parthenium hysterophorus Linn phytochemically and pharmacologically. Phytochemical screening is important for the isolation of active compounds before bulk extraction. The crude extracts and their fractions were screened for enzyme (urease, α-glycosidase, and phosphodiesterase) inhibition assays, in vivo analgesic, anti-inflammatory, and sedative effects. Results indicated the presence of steroids, flavonoids, etc. The crude extracts such as methanol, hexane, aqueous, ethyl acetate, chloroform, and butanol exhibited excellent urease inhibitory activities with IC50 = 43.1 ± 1.24, 31.9 ± 2.21, 31.9 ± 2.21, 57.3 ± 1.27, 49.2 ± 2.16, and 35.3 ± 1.12, respectively, as compared to standard acetohydroxamic acid (20.3 ± 0.43). The extracts (methanol, hexane, aqueous, ethyl acetate, chloroform, and butanol) also showed promising α-glycosidase potency with IC50 = 13.1 ± 0.34, 21.2 ± 1.16, 23.1 ± 0.12, 84.2 ± 2.17, 118.6 ± 3.07, and 840 ± 1.73, respectively against acarbose (840 ± 1.73). The phosphodiesterase activity of the mentioned extracts was also excellent with IC50 = 131.1 ± 2.41, 197.2 ± 3.16, 24.2 ± 0.11, 62.4 ± 2.21, 152.4 ± 1.81, and 55.3 ± 2.15, respectively, against the standard (265.5 ± 2.25). Furthermore, butanol (14.96 ± 1.78), ethyl acetate (18.98 ± 1.71), and methanol (16.87 ± 1.00) showed dose-dependent analgesic effects with a maximum inhibition of acetic acid-induced writhes. Whereas, methanolic and butanol extracts exhibited maximum inhibition of inflammation in the carrageenan paw edema test. The aqueous (p < 0.01) and butanol (p < 0.01) extracts exhibited maximum a sedative effect followed by chloroform (p < 0.05), ethyl acetate (p < 0.05), and methanolic (p < 0.05) fractions as compared to the standard drug. The current research concluded that Parthenium hysterophorus Linn has important phytochemical constituents having inhibitory effects on urease, α-glycosidase, and phosphodiesterase enzymes. Furthermore, the plant has analgesic, anti-inflammatory, and sedative effects. The P. hysterophorus needs to further be explored for the candidate molecules responsible for the abovementioned activities.

In Vivo Study on Analgesic, Muscle-Relaxant, Sedative Activity of Extracts of Hypochaeris radicata and In Silico Evaluation of Certain Compounds Present in This Species.

BACKGROUND: Hypochaeris radicata (flatweed) from the family Asteraceae is a medicinal plant found in Europe, Middle East, and India. In folkloric medication, it is used to heal jaundice, dyspepsia, constipation, rheumatism, and hypoglycemia as well as renal problems. Leaves and roots of the plant have antioxidant and antibacterial properties. The plant is a rich source of pharmacologically active phytochemicals; however, it is explored scantily. The objective of the current study was to identify the chemical composition and investigate the in vivo biological potency of crude extracts of this plant. METHODS: The crude extract and the fractions were screened for various phytochemical groups of constituents following standard procedures. The acute toxicity was assayed for safe range of dose determination. The analgesic potential of the extract and fractions was assessed by acetic acid-induced writhing test. The muscle-relaxant activity was examined by standard inclined-plane test and traction test. Sedative potential of extract/fractions was assessed by using standard white wood procedures. Furthermore, docking analysis of two compounds present in the ethyl acetate fraction of the plant was assessed against 3D cyclooxygenase-1 and -2 (COX-1 and COX-2). RESULTS: The extract/fractions of H. radicata showed significant analgesic effect in in vivo model of peripheral algesia. The docking analysis of previously isolated molecules from the plant also exhibited promising interaction with COX-1 and COX-2. Also, the plant has a mild sedative and muscle-relaxant potential. Thus, our study provided pharmacological rationale for the traditional uses of the plant as analgesic and anti-inflammatory remedy. CONCLUSION: The crude extracts and fractions exhibited excellent activity due to active phytochemicals. These active phytochemicals also exhibited promising interaction with COX-1 and COX-2. These findings directed researcher to isolate active compounds from H. radicata which may be used as a potential source of active secondary metabolites.

Antinociceptive and anti-inflammatory activities of flavonoids isolated from Pistacia integerrima galls.

The present study deals with the anti-hyperalgesic and anti-inflammtory effects of flavonoids (1-4) isolated from the chloroform fraction of Pistacia integerrima galls. The structure of isolated compounds was elucidated by using advance spectroscopy analysis and comparing their physical spectral data with reported one. The pretreatment of compounds (1-4) caused significant anti-hyperalgesic effects in acetic acid induced writhing test in a dose dependent manner. The compounds strongly complimented the effects in both phases of formalin test. However, the administration of naloxone did not abolish the induced antinociceptive effects and therefore suggested the absence of opioid receptor involvement. The pretreatment of flavonoids (1-4) elicited marked anti-inflammtory effects in carrageenan induced paw edema test in mice during various assessment times (1-5 h). The effects were dose dependent and maximum results were observed after 3rd h of treatments which remained significant up to 5th hour. It is concluded that the isolated flavonoids (1-4) possessed strong anti-hyperalgesic and anti-inflammtory activity and thus are strong candidates for further detail studies.

Biological Evaluation and Docking Analysis of Daturaolone as Potential Cyclooxygenase Inhibitor.

This study deals with the isolation of the active constituent(s) from a methanolic extract of Pistacia integerrima J. L. Stewart barks and it was also oriented to evaluate the in vivo and in silico anti-inflammatory activity. By NMR and crystallography techniques, we have isolated a triterpenoid identified as daturaolone (compound 1). This compound showed in vivo a significant and dose dependent (1-30 mg/kg) anti-inflammatory activity on carrageenan-induced mouse paw oedema (ED50 = 10.1 mg/kg) and on acetic acid-induced writhing responses in mice (ED50 = 13.8 mg/kg). In the in vivo experiments, the effect of tested compound was also evaluated in presence of the reference drug diclofenac (1-30 mg/kg). Moreover, in silico analysis of receptor ligand complex shows that compound 1 interacts with cyclooxygenases (COXs) binding sites displaying an interesting interaction with COX-1. These findings suggest that compound 1 isolated from P. integerrima possesses in vivo anti-inflammatory and antinociceptive potentials, which are supported in silico by an interaction with COXs receptors.

Anti-nociceptive, anti-inflammatory and sedative activities of the extracts and chemical constituents of Diospyros lotus L.

Diospyros lotus L. is traditionally used in various diseases including pain and sleep disorders. The pain and inflammation are the common problems, which are treated with various synthetic analgesic drugs, and associated the side effects. The natural products have gained significant importance over synthetic drugs. The importance of phyto-medicine the current study has been designed with the aim to investigate the analgesic and anti-inflammatory effects of Diospyros lotus and bioassay guided isolation from its crude fractions. Seven known compounds; lupeol (1), 7-methyljuglone (2), ß-Sitosterol (3), stigmasterol (4) betulinic acid (5), diospyrin (6; DS) and 8-hydroxyisodiospyrin (7; HDS) which were hitherto unreported from D. lotus. The chloroform fraction (CFDL) and isolated compounds DS and HDS were evaluated for anti-nociceptive, sedative and anti-inflammatory effects. The acetic acid induced writing was significantly (p<0.001) protected by CFDL (72.43%), DS (40.87%) and HDS (65.76%) at higher doses which exhibited peripheral and central analgesic effects in acetic acid and hot-plat pain paradigms. Regarding the anti-inflammatory effect the CFDL (77.43%), DS (80.54%) and HDS (75.87%) protected the carrageenan paw edema after 3rd h. The central analgesic effect was significantly antagonized with naloxone (0.5 mg/kg), showing opiodergic mechanism of action. The CFDL, DS and HDS were also proved sedative in open field animal models. In acute toxicity study the chloroform fraction [CFDL (50, 100 and 150 mg/kg)], DS (5 and 10 mg/kg) and HDS (5 and 10 mg/kg) were found safe. Our study concluded that CFDL, DS and HDS have marked anti-nociceptive, anti-inflammatory and sedative effect. The anti-nociceptive and anti-inflammatory effects of the roots of D. lotus are partially attributed due to the presence of analgesic constituents like diospyrin (DS), 8-hydroxyisodiospyrin (HDS) and strongly supports the ethno-pharmacological uses of D. lotus as anti-nociceptive, anti-inflammatory and sedative.