Research progress on natural guaiane-type sesquiterpenoids and their biological activities / 中国中药杂志

Guaiane-type sesquiterpenoids are a class of terpenoids with [5,7] ring-fused system as the basic skeletal structure composed of three isoprene units, which are substituted by 4,10-dimethyl-7-isopropyl. According to the difference in functional groups and degree of polymerization, they can be divided into simple guaiane-type sesquiterpenoids, sesquiterpene lactones, sesquiterpene dimers, and sesquiterpene trimers. Natural guaiane-type sesquiterpenoids are widely distributed in plants, fungi, and marine organisms, especially in families such as Compositae, Zingiberaceae, Thymelaeaceae, Lamiaceae, and Alismataceae. Guaiane-type sesquiterpenoids have good antibacterial, anti-inflammatory, anticancer, and neuroprotective effects. In this paper, the novel guaiane-type sesquiterpenoids isolated and identified in recent 10 years(2013-2022) and their biological activities were reviewed in order to provide refe-rences for the research and development of guaiane-type sesquiterpenoids.

New di-spirocyclic labdane diterpenoids from the aerial parts of Leonurus japonicus / 中国天然药物

Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids (1-18). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones (1-6), two new (7 and 8) and six known (13-18) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative (9), and three new ones incorporating a γ-lactone unit (10-12). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.

Meroterpenoids from Rhododendron nivale / 中国中药杂志

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.

Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron / 中国天然药物

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 μmol·L-1.

Reviews on natural monocyclic sesquiterpenoids and their bioactivities / 中国中药杂志

Sesquiterpenes are a class of terpenoids composed of three isoprene units( 15 carbons). Sesquiterpenoids possess a variety of different structures,including acyclic sesquiterpenes,monocyclic sesquiterpenoids,bicyclic sesquiterpenoids,tricyclic sesquiterpenoids,tetracyclic sesquiterpenoids and macrocyclic sesquiterpenoids. Among them,a large number of monocyclic sesquiterpenoids were isolated and display extensive bioactivities,such as cytotoxic,antioxidant,anti-inflammatory,antibacterial and other activities. In this review,we summarized the progress about the phytochemistry and biological activities of monocyclic sesquiterpenoids( a total of161 compounds) reported from 2014 to 2018( 5 years),including megastigmanes,monocyclofarnesol-type,bisabolane-type,germacrane-type,and other types of monocyclic sesquiterpenoids. Furthermore,several future research perspectives and development of sesquiterpenoids as potential therapeutic agents were discussed as well.

Construction, expression, purification and neuroprotective activity of TAT-FGF21 fusion protein / 中国药科大学学报

@#In order to improve the brain distribution of fibroblast growth factor 21(FGF21), TAT-FGF21 fusion protein was designed and its neuroprotective activity was investigated. The recombinant plasmid of pET28a-TAT-FGF21 was constructed and transformed into E. coli BL-21(DE3)sensitive bacteria. The TAT-FGF21 fusion protein was purified by Ni-NTA affinity chromatography column after IPTG induced expression. The SH-SY5Y cell damage model was induced by Aβ25-35, and the TAT-FGF21 fusion protein was used to intervene. The effects of Aβ25-35 and TAT-FGF21 induced on SH-SY5Y cell viability were determined using MTT method; DCFH-DA fluorescent probe was used to detect the intervention effect TAT-FGF21 on reactive oxygen species(ROS)generation induced by Aβ25-35 in SH-SY5Y cells; the effects of Aβ25-35 and TAT-FGF21 on mitochondrial membrane potential in SH-SY5Y cells were detected with JC-1 fluorescent probe. The results showed that TAT-FGF21 could improve the viability of SH-SY5Y cells, reduce the intracellular ROS production level of SH-SY5Y cells, and enhance the mitochondrial membrane potential of SH-SY5Y cells, which indicate that TAT-FGF21 could protect neurons on SH-SY5Y cell injury induced by Aβ25-35 through alleviating oxidative damage.

Research progress on chemical structures and pharmacological effects of natural aucubin and its derivatives / 中草药

Aucubin, one of natural active constituents, is widely distributed in Chinese materia medica, such as Scrophularia ningpoensis, Eucommia ulmoides, Plantago depressa and so on, and its pharmacolagical activities have been paid more and more attention. Nevertheless, aucubin derivatives are rarely reported. In this review, the chemical constituents of aucubin derivatives mainly included 6-O-substituent type, 10-O-substituent type, 6,10-O-disubstituent type, 6′-O-substituent type and other types, meanwhile, their pharmacological activities, such as anti-oxidant, anti-inflammatory, antibacterial, neuroprotective and antitumor activities, were summarized in the recent 10 years.

Neuroprotective activity of two active chemical constituents from Tinospora hainanensis

OBJECTIVE@#To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro.@*METHODS@#The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS. Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines. Cell morphology of treated PC12 cells was observed by phase contrast microscopy. In-vitro MTT assay, lactate dehydrogenase activity assay and oxidative stress markers (intracellular ROS production, MDA level, and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells.@*RESULTS@#The two new compounds, named Tinosporaic acid A and B, were isolated and identified from the stem bark of Tinospora hainanensis. Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers. Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide, thus promoting PC12 cells survival. The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively, which is neuroprotective for EC50. The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity.@*CONCLUSION@#The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.

Neuroprotective activity of two active chemical constituents from Tinospora hainanensis

Objective To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro. Methods The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS. Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines. Cell morphology of treated PC12 cells was observed by phase contrast microscopy. In-vitro MTT assay, lactate dehydrogenase activity assay and oxidative stress markers (intracellular ROS production, MDA level, and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells. Results The two new compounds, named Tinosporaic acid A and B, were isolated and identified from the stem bark of Tinospora hainanensis. Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers. Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide, thus promoting PC12 cells survival. The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively, which is neuroprotective for EC50. The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity. Conclusion The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.

Chemical constituents from stems of Clausena emarginata / 中草药

Objective: To investigate the chemical constituents from the stems of Clausena emarginata. Methods: The compounds were isolated by macroporous resin, silica gel, ODS column chromatography, Sephadex LH-20, reversed-phase MPLC, and then purified by preparative HPLC. Their structures were determined by the analysis of ultraviolet spectrum, mass spectrum, and NMR spectrum. Neuroprotective activities of compounds 11 and 12 were initially investigated. Results: Sixteen compounds were isolated from the petroleum ether and acetone fractions of 95% ethanol extract of the stems of Cl. emarginata, and their structures were identified as 1H-Indole-3-carboxaldehyde (1), E-N-benzoiltiramine (2), dehydrodiconiferyl alcohol (3), tortoside A (4), zhebeiresinol (5), evofolin B (6), 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (7), echipuroside A (8), 3-methylcarbazole (9), murrayafoline A (10), clausine Z (11), indizoline (12), clausenaline B (13), mafaicheenamine A (14), dictamnine (15), and honokiol (16). Conclusion: Compounds 1-8 are isolated from the plants of genus Clausena L. for the first time, compounds 1-16 are isolated from this plant for the first time. Compounds 11 and 12 show the neuroprotective activity against rotenone induced PC12 cell damage.

Chemical constituents of Cremastra appendiculata and their neuroprotection / 中草药

Objective: To study the chemical constituents of Cremastra appendiculata and their neuroprotection. Methods: The chemical constituents were separated and purified by silica gel, Sephadex LH-20 column chromatography, ODS column chromatography, and HPLC column chromatography. Their structures were determined by NMR spectrum. Results: Applying various chromatographic separation methods, 23 compounds were obtained from the aceticether extraction of 55% ethanol extract of C. appendiculata. Based on physicochemical properties and spectroscopic analysis, 20 structures were identified as miltarine (1), 1-(4-β-D-glucopyranosyloxybenzyl)-2-isobutylmalate-4-methyl (2), 1-[4-(β-D-glucopyranosyloxy)benzyl]-4-methyl-2-benzylmalate (3), batatasin III-3-O-glucoside (4), eucomic acid (5), hesperidin (6), (4-methyl-1,3-phenylene) dicarbamic acid methyl ester (obtucarbamate A) (7), (3-meth-oxycarbonylamino-2-methyl-phenyl)-cabamic acid metylester (8), 4,4'-diphenylmethanebis(methyl) carbamate (9), 3,3'-dihydroxy-2',6'-bis(p-hydroxybenzyl)-5-methoxybibenzyl (10), 3',5-dihydroxy-2-(4-hydroxybenzyl)-3-methoxybibenzyl (11), 3,3'-dihydroxy-2-(4-hydroxybenzyl)-5-methoxybibenzyl (12), corylin (13), batatasin III (14), neobavaisoflavone (15), isobavachalcone (16), 2,6,2',6'-tetramethoxy-4,4-bis(2,3-epoxy-1-hydroxypropyl)biphenyl (17), coelonin (18), gigantol (19), and β-sitosterol (20). Conclusion: Compounds 7-9, 13, and 15-17 are obtained from the plants of Cremastra Lindl. for the first time. Compounds 5 and 6 are obtained from the plant for the first time. Compounds 1 and 17 have the good performance of neuroprotection in hydrogen peroxide model. Neuroprotective mechanism is likely to be achieved by weakening the oxidative damage.

Caffeic acids from roots of Arctium lappa and their neuroprotective activity / 中草药

Objective: To investigate the caffeic acid compounds from the roots of Arctium lappa and their neuroprotective activity. Methods: The compounds were isolated by column chromatography over silica gel, octadecylsilane (ODS) chemically bonded silica gel, Sephadex LH-20, and AB-8 macroporous resin coupled with preparative HPLC. Their structures were elucidated by spectroscopic analysis and their neuroprotective activity against glutamate-induced neurotoxicity was evaluated in SH-SY5Y cells by MTT assay. Results: Eight caffeic acid compounds were isolated from the roots of A. lappa, which were identified as 1,5-O-dicaffeoyl-3-O-(4-malic acid methyl ester)-quinicacid (1), 3,5-O-dicaffeoyl-quinic acid methyl ester (2), 3,4-O-dicaffeoyl-quinic acid methylester (3), 4,5-O-dicaffeoyl-quinic acid methyl ester (4), (2E)-1,4-dimethyl-2- [(4-hydroxyphenyl)methyl]-2-butenedioicacid (5), chlorogenic acid methyl ester (6), caffeic acid mtheyl ester (7), and 3,4,3',4'-tetrahydroxy-δ-truxinate (8). In vitro, these compounds showed the neuroprotective activity against glutamate-induced neurotoxicity on different levels. Conclusion: The neuroprotective activity of the roots in A. lappa against glutamate-induced neurotoxicity is related to the caffeic acid compounds. Compound 1 is a new compound; Compound 5 is a new natural compound; Compounds 2-4 and 6-7 are isolated from A. lappa for the first time; Compound 8 is isolated from the plants of Arctium L. for the first time.

Neuroprotective Effect of Steamed and Fermented Codonopsis lanceolata

Codonopsis lanceolata has been used as an herbal medicine for several lung infl ammatory diseases, such as asthma, tonsillitis, and pharyngitis. Previously, we showed the neuroprotective effect of steamed and fermented C. lanceolata (SFC) in vitro and in vivo. In the current study, the treatment of HT22 cells with SFC decreased glutamate-induced cell death, suggesting that SFC protected HT22 cells from glutamate-induced cytotoxicity. Based on these, we sought to elucidate the mechanisms of the neuroprotective effect of SFC by measuring the oxidative stress parameters and the expression of Bax and caspase-3 in HT22 cells. SFC reduced contents of ROS, Ca2+ and NO. Moreover, SFC restored contents of glutathione and glutathione reductase as well as inhibited Bax and caspase-3 activity in HT22 cells. These results indicate that steamed and fermented C. lanceolata (SFC) extract protected HT22 cells by anti-oxidative effect and inhibition of the expression of Bax and caspase-3.