Norbergenin

Elucidation of reactive oxygen species scavenging pathways of norbergenin utilizing DFT approaches.[Pubmed:36569231]

R Soc Open Sci. 2022 Dec 21;9(12):221349.

Bergenin is a polyphenolic compound that contains isocoumarin skeletal derived from C-glycosylated 4-O-methylgallic acid. The biological activities of this compound and its derivatives are quite diverse. Recent studies reveal neuroprotective effects in vitro and in vivo in Alzheimer's. Norbergenin is a demethylated form of bergenin, known for better antioxidant capacity and associated with neuroprotective properties through oxidative stress inhibition. This study focused on investigating the scavenging mechanism of Norbergenin with the (*)OH, (*)OOH, and O2∙- as a radical model under physiological and lipid environments. The thermodynamic and kinetic parameters of the hydrogen transfer (HT), single electron transfer (SET), sequential proton lost-electron transfer (SPLET) and radical adduct formation (RAF) mechanisms were determined theoretically by the density functional theory (DFT) at M06-2X/6-311 + + G(d,p) level of theory. Based on the computational results, this compound has proved as an excellent (*)OOH and (*)OH scavenger under physiological conditions better than Trolox and vitamin C, whereas its radical demonstrated as an efficient O2∙- scavenger.

Unveiling major ethnopharmacological aspects of genus Diospyros in context to its chemical diversity: A comprehensive overview.[Pubmed:36136087]

J Food Biochem. 2022 Dec;46(12):e14413.

Diospyros species (DS), "Ebenaceae," were known for their therapeutic uses in folk medicine since days of yore. Thereafter, scientific evidence related their health benefits to a myriad of chemical classes, for instance, naphthoquinones, flavonoids, tannins, coumarins, Norbergenin derivatives, sterols, secoiridoids, sesquiterpenes, diterpenoids, triterpenoids, volatile organic compounds (VOCs), and carotenoids. The available literature showed that more than 200 compounds were isolated and identified via spectroscopic techniques. Many pharmacological activities of DS have been previously described, such as antioxidant, neuroprotective, antibacterial, antiviral, antiprotozoal, antifungal, antiinflammatory, analgesic, antipyretic and cosmeceutical, investigated, and confirmed through versatile in vitro and in vivo assays. Previous studies proved that genus Diospyros is a rich reservoir of valuable bioactive compounds. However, further comparative studies among its different species are recommended for more precise natural source-based drug discovery and clinical application. Accordingly, this review is to recall the chemical abundance and diversity among different members of genus Diospyros and their ethnopharmacological and pharmacological uses. PRACTICAL APPLICATIONS: Practically, providing sufficient background on both secondary metabolites divergence and pharmacological properties of genus Diospyros has many fruitful aspects. As demonstrated below, extracts and many isolated compounds have significant curative properties, which can lead to the discovery of pharmaceutically relevant alternative substitutes to conventional medicine. Consequently, molecular docking on various receptors can be applied. On the grounds, Naoxinqing tablets, a standardized herbal product containing D. kaki leaves extract, have been patented and recorded in Chinese Pharmacopeia as an approved Traditional Chinese Medicine (TCM) for the treatment of cerebro- and cardiovascular diseases, although the underlying mechanism remains under advisement. Moreover, the antimicrobial applications of DS are of considerable concern; since the widespread use of antibiotics resulted in different forms of bacterial resistance, hence, limiting and compromising effective treatment. In addition, as a result of contemporary rampant memory disorders, neuroprotective activities of different extracts of DS became of great emphasis.

Studies on Quality Markers of Kaihoujian Spray for Anti-Inflammation Based on Gray Correlation Analysis Strategy.[Pubmed:35497922]

Evid Based Complement Alternat Med. 2022 Apr 20;2022:1273066.

Kaihoujian spray (KHJ) was originated from the classical prescription of Miao medicine, which was commonly used for acute and chronic pharyngitis. The prescription was composed of Sophorae Tonkinensis Radix, Ardisiae Radix, Cicadae Periostracum, and menthol. However, in previous literature, only clinical studies have been reported. The Quality Marker (Q-Markers) of KHJ on anti-inflammation has not been clearly elucidated. In this study, a gray correlation analysis strategy combined with network pharmacology analysis was established for the investigation of Q-Markers in KHJ. A total of 52 components were identified or tentatively characterized in KHJ, including alkaloids, saponins, bergenin, flavonoids, amino acids, and their derivatives. Furthermore, regularity of recipe composition and gray correlation analysis revealed that the correlation degree of all peaks was greater than 0.5. The ranking of correlation degree was peak 1 > 6>9 > 8>7 > 10>4 > 5>11 > 3>2. Among them, peaks 2, 4, 5, 6, 8, 9, and 11 were identified as anagyrine, matrine, sophocarpine, Norbergenin, bengenin, 11-O-galloylbergenin, and trifolirhizin. The network pharmacology analysis revealed that EGFR, MMP9, MMP3, MMP1, and PTGS2 were the main targets of KHJ. Bergenin, matrine, sophocarpine, calycosin, and trifolirhizin were the main anti-inflammatory active ingredient in KHJ. These results proposed that bergenin, sophocarpidine, sophocarpine, and trifolirhizin could be the Q-Markers of KHJ on anti-inflammation. The process of discovering the Q-Markers would provide a promising method of quality control on KHJ.

Contribution of Flavonoids and Iridoids to the Hypoglycaemic, Antioxidant, and Nitric Oxide (NO) Inhibitory Activities of Arbutus unedo L.[Pubmed:32098404]

Antioxidants (Basel). 2020 Feb 22;9(2):184.

This study aims at investigating the contribution of two classes of compounds, flavonoids and iridoids, to the bioactivity of Arbutus unedo L. leaves and fruits. The impact of different extraction procedures on phytochemicals content and hypoglycemic, antioxidant, and nitric oxide (NO) inhibitory activities of A. unedo fresh and dried plant materials was investigated. Ellagic acid 4-O-beta-D-glucopyranoside, kaempferol 3-O-glucoside, and Norbergenin were identified for the first time in this genus by using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS). Three iridoids (gardenoside, geniposide, unedoside) are specifically identified in the leaves. Interestingly, asperuloside was extracted only from dried fruits by ethanol with Soxhlet apparatus. Extracts were screened for their potential antioxidant activities by using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Activity Power (FRAP), and beta-carotene bleaching tests. Based on the Global Antioxidant Score (GAS) calculation, the most promising antioxidant extract was obtained by hydroalcoholic maceration of dried leaves that showed half maximal inhibitory concentration (IC(50)) of 0.42 and 0.98 mug/mL in ABTS and DPPH assays, respectively. The hypoglycaemic activity was investigated by alpha-amylase and alpha-glucosidase inhibition tests. Extracts obtained by ethanol ultrasound extraction of fresh leaves and hydroalcoholic maceration of fresh fruits (IC(50) of 19.56 and 28.42 mug/mL, respectively) are more active against alpha-glucosidase than the positive control acarbose (IC(50) of 35.50 mug/mL). Fruit extracts exhibited the highest anti-inflammatory activity.

Water-soluble extract of Saxifraga stolonifera has anti-tumor effects on Lewis lung carcinoma-bearing mice.[Pubmed:27575479]

Bioorg Med Chem Lett. 2016 Oct 1;26(19):4671-4678.

Saxifraga stolonifera is an evergreen and herbaceous plant well known in Korea, Japan and western China, which has great potential applications in gardening and pharmacology. The aim of this study is to evaluate the anti-tumor effects of S. stolonifera extraction on lung tumors of Lewis mice. By the measurement of MS/MS, we found that there were four main bioactive components in methanol extract of S. stolonifera, including gallic acid, Norbergenin, protocatechuic acid and bergenin, and the results of quantitative analysis showed that the contents of gallic acid, protocatechuic acid and bergenin in methanol extract of S. stolonifera were 5.150, 1.492, 24.559mg/g, respectively. Animal experiment showed that the mean tumor weight of Lewis lung carcinoma-bearing mice treated with water-soluble extract of S. stolonifera was obviously smaller than model group (cis-DDP), and its inhibition rate was 49.2%. In addition, histopathological evaluation and immunohistochemical assay confirmed the anti-tumor effects of S. stolonifera. Investigation of four haematological parameters revealed that the Lewis mice fed with S. stolonifera showed good resilience in the level of leukocyte, haemoglobin, blood platelets and red blood cell compared with the model group. In addition, RT-PCR suggested that the relative expression of pro-apoptosis gene p53, Sox and Bax was enhanced, while the relative expression of anti-apoptosis gene Bcl2 was diminished in comparison with model group. These results suggested that water-soluble extract of S. stolonifera has anti-tumor effects on Lewis lung tumors.

Chemical components from the leaves of Ardisia insularis and their cytotoxic activity.[Pubmed:25794927]

Arch Pharm Res. 2015 Nov;38(11):1926-31.

One new oleanane triterpene glycoside, ardinsuloside (1), and twelve known compounds, demethoxybergenin (2), Norbergenin (3), bergenin (4), 4-O-galloylbergenin (5), quercitrin (6), myricitrin (7), myricetin 3-O-(3''-O-galloyl)-alpha-L-rhamnopyranoside (8), desmanthine-2 (9), epicatechin 3-O-galloyl ester (10), 3'-methoxyepicatechin 3-O-galloyl ester (11), gallic acid (12), and methyl galloate (13) were isolated from the leaves of Ardisia insularis. Their structures were established on the basis of spectral and chemical evidence, which were in agreement with those reported in literature. The cytotoxic activities of these compounds were evaluated on three cancer cell lines namely A-549 (human lung cancer), HT-29 (Human colon adenocarcinoma), and OVCAR (human ovarian carcinoma). The results revealed that compound 1 inhibited A-549, HT-29, and OVCAR cell lines with IC50 values of 8.5 +/- 1.2, 16.4 +/- 3.1, and 13.6 +/- 2.4 muM, respectively. The remaining compound showed weak cytotoxic activity. This result indicated that compound 1 could be useful in the treatment of cancer disease.

[Chemical constituents from Glechoma longituba].[Pubmed:25204149]

Zhongguo Zhong Yao Za Zhi. 2014 Feb;39(4):695-8.

Fourteen compounds were obtained from Glechoma longituba by the chromatographic methods of silica gel, ODS, Sephadex LH-20 and preparative of HPLC. According to physicochemical properties and spectral data, these compounds were identified as stilbostemin B (1), trilepisiumic acid (2), 3, 4-dihydroxyphenyl ethanol ketone (3), bergeninmonohydrate (4), oresbiusin A (5), Norbergenin (6), stilbostemin D (7), ehretioside B (8), ethyl ferulate (9), E-p-hydroxy-cinnamic acid (10), methyl gallate (11), protocatechuic acid (12), 4'-Hydroxyacetophenone (13), and E-3-2,4-dihydroxyphenyl-2-acrylic acid (14). Among them, compounds 1-10, 13 and 14 were isolated from this plant for the first time.

Norbergenin derivatives from Diospyros crassiflora (Ebenaceae).[Pubmed:24427945]

Nat Prod Commun. 2013 Nov;8(11):1575-8.

From the ethyl acetate extract of the stems of Diospyros crassiflora Hiern, three new Norbergenin derivatives, 4,11-di-O-galloylNorbergenin (1), 3-O-galloylNorbergenin (2), and 4-O-(4'-hydroxy-3'-methoxybenzoyl)-Norbergenin (3), were isolated along with ten known compounds (4-13). Their structures were established by mean of spectroscopic techniques namely 1- and 2-D NMR experiments, mass spectrometry and comparison with reported data. Isolates 1-9 were evaluated for their ability to protect PC12 cells against hydrogen peroxide induced injury. Compounds with a galloyl group in their structure were found to prevent toxicity induced by H2O2 in PC12 cells.

Synthesis, antioxidant capacity, and structure-activity relationships of tri-O-methylnorbergenin analogues on tyrosinase inhibition.[Pubmed:24268551]

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6580-4.

A series of tri-O-methylNorbergenin analogues 1-9 were synthesized and their antioxidant activities and inhibitory effects on tyrosinase were evaluated. Among tested analogues, compound 4 bearing cathechol moiety exhibited greater antioxidant activity and excellent inhibition on tyrosinase with IC50 value of 9.1 muM, comparable to that of corresponding positive controls. The inhibition mechanism analysis of compound 4 demonstrated that it was a mixed-type inhibitor on tyrosinase. These results suggest that these compounds may serve as a useful clue for further designing and development of novel potential tyrosinase inhibitors.

[Bergenia genus - content matters and biological activity].[Pubmed:23256653]

Ceska Slov Farm. 2012 Oct;61(5):203-9.

Bergenia, a genus included in the family Saxifragaceae, is a valuable source of healing matters. About 30 Bergenia species are known all over the world. Scientific research is focused on five species mainly distributed in the mountains of Central and East Asia: Bergenia ciliata (Haw.) Sternb., Bergenia stracheyi Engl., Bergenia crassifolia (L.) Fritsch, Bergenia ligulata (Wall.) Engl. and Bergenia himalaica Boriss. These taxons belong to the widely used medicinal herbs in the traditional Chinese, Nepalese and Indian medicine, for therapy of cough and pulmonary diseases, to stop bleeding, to increase immunity and to dissolve kidney or bladder stones. Bergenia consists of many different active compounds including bergenin, Norbergenin, catechin, gallic acid, arbutin and other polyphenols. In the Czech Republic this species is commonly grown but it is not used for medical therapy. Individual parts of this plant demonstrate an interesting biological activity, and antibacterial, antiviral, cytoprotective and antioxidant effects.

Two new antioxidant bergenin derivatives from the stem of Rivea hypocrateriformis.[Pubmed:21406219]

Fitoterapia. 2011 Jun;82(4):722-5.

Two new bergenin derivatives, named rivebergenin A and B (1, and 2), together with two known compounds, bergenin (3) and Norbergenin (4) were isolated from the stem of Rivea hypocrateriformis (Desr.) Choisy. The structures of the new compound have been assigned from (1)H and (13)C NMR spectra, DEPT, and by 2D COSY, HMQC, and HMBC experiments. Compounds 1-4 showed the strong antioxidant activity.

Antimalarial activity of extract and norbergenin derivatives from the stem bark of Diospyros sanza-minika A. Chevalier (Ebenaceae).[Pubmed:21031627]

Phytother Res. 2010 Nov;24(11):1676-9.

The methanol extract from the stem bark of Diospyros sanza-minika as well as five Norbergenin derivatives isolated from this crude extract were evaluated for their in vitro activity against Plasmodium falciparum K1 and cytotoxicity on MRC-5 cells. 4-O-(3'-methylgalloyl)Norbergenin was found to be the most potent compound (IC(50) 0.6 mug/mL; CC(50) 24.7 mug/mL), followed by 4-O-galloylNorbergenin (IC(50) 3.9 mug/mL; CC(50) > 64 mug/mL) and 11-O-p-hydroxy-benzoyl-Norbergenin (IC(50) 4.9 mug/mL; CC(50) > 64 mug/mL). Norbergenin and 4-O-syringoylNorbergenin were inactive (IC(50) > 32 mug/mL; CC(50) > 64 mug/mL). The antimalarial activity of the pure constituents and of the methanol extract from the stem bark of Diospyros sanza-minika is reported for the first time. The results provide interesting baseline information for the potential use of the crude extract well as some of the isolated compounds in the search for novel antimalarial compounds.

Comparative in vitro bioactivities of tea extracts from six species of Ardisia and their effect on growth inhibition of HepG2 cells.[Pubmed:20561930]

J Ethnopharmacol. 2010 Aug 9;130(3):536-44.

AIM OF THE STUDY: Ardisia species, notably A. compressa, are used in some regions of the world as food or in traditional medicine for prevention and treatment of certain health conditions including liver disease. We investigated the chemical composition and relative anticancer potential of six Ardisia species [A. japonica (AJ), A. escallonioides (AES), A. mamillata (AM), A. compressa (AC), A. crenata (ACR), and A. elliptica (AE)]. MATERIALS AND METHODS: Antioxidant capacity, DNA human topoisomerase II catalytic inhibition, and cytotoxicity on human liver cancer cells (HepG2) were determined in vitro in tea extracts of the 6 Ardisia species evaluated. Selected pure phenolic compounds present in Ardisia species were also evaluated. RESULTS: AC showed the highest topoisomerase II catalytic inhibition (IC(50)=12 microg/ml) and cytotoxicity (IC(50)=117 microg/ml) against HepG2 cells, followed by ACR and AJ. Total polyphenols ranged from 21 to 72 mg equivalents of gallic acid (GA)/g solid extract (SE). LC-MS analysis revealed the presence of GA, quercetin derivatives, ardisenone, ardisiaquinone, ardisianone, bergenin, Norbergenin, and embelin. However, neither total polyphenol concentration nor antioxidant capacity correlated with anticancer capacity. Significant HepG2 cytotoxicity was also achieved by bergenin (IC(50)=18 microM) and embelin (IC(50)=120 microM). AC, bergenin, embelin, and quercetin showed a tendency to accumulate cells in the G1 phase and reduced G2/M leading to apoptosis. CONCLUSIONS: Although the mechanism is not entirely clear, AC, ACR, and AJ are the Ardisia species with the greatest anticancer potential against liver cancer cells in vitro and deserve further investigation.

Immunomodulatory effect of bergenin and norbergenin against adjuvant-induced arthritis--a flow cytometric study.[Pubmed:17408893]

J Ethnopharmacol. 2007 Jun 13;112(2):401-5.

Bergenin (1), a C-glycoside of 4-O-methyl gallic acid, isolated from rhizomes of Bergenia stracheyi (Saxifragaceae) and its O-demethylated derivative Norbergenin (2), prepared from 1, are reported to show anti-arthritic activity through possible modulation of Th1/Th2 cytokine balance. Flow cytometric study showed that the oral administration of 1 and 2 at doses of 5, 10, 20, 40 and 80 mg/kg per oral dose inhibit the production of proinflammatory Th1 cytokines (IL-2, IFN-gamma and TNF-alpha) while as potentiate anti-inflammatory Th2 cytokines (IL-4 and IL-5) in the peripheral blood of adjuvant-induced arthritic balb/c mice. This shows the potential Th1/Th2 cytokine balancing activity of 1 and 2 which is strongly correlated with their anti-arthritic activity. At similar dose levels, the effect of 2 was found to be more than that of 1. The oral LD(0) for 1 and 2 was more than 2000 mg/kg body weight of the mice.