Although great progress continues to be made against cancer, it remains the second leading cause of death in the world. As pointed out in the World Cancer Report 2014, elucidating the causes and devising effective prevention strategies are essential components of cancer control. Hence, in this review, we focus on effective and safe cancer chemopreventive reagents, which could reverse the processes of initiation and subsequent progression of cancer.Natural products from traditional herbals and food, consumed with years of history, have attracted much attention because of their safety, efficacy, and potency for cancer chemoprevention. Based on 119 references, we collected 179 chemopreventive phytochemicals, including flavonoids, terpenoids, alkaloids, phenylpropanoids, and stilbenes. In our recent research, we have also reported a series of novel chemopreventive reagents from Traditional Chinese Medicines and functional food.This review has summarized the latest research on the bioactive natural products reported as chemopreventive reagents in vitro or in vivo. The research results could throw light on further study for accurate prevention strategies against cancer. Furthermore, the functional factors from the food suggested more healthful dietary pattern for the special group.

•The anti-neuroinflammatory material basis of C. turfanensis was characterized.•Brief SAR between the constituents and anti-neuroinflammatory activities was discussed.•Caraganolide A and 3′,7,8-trihydroxy-4′-methoxyisoflavone were suggested to be potential neuroinflammatory inhibitors.Because of the critical role of over-activated microglia in the progress of neurodegenerative diseases, it has been selected as a potential therapeutic target for drug discovery. In order to find natural neuroinflammatory inhibitors, we carried out a bioactivity-oriented phytochemical research of Caragana turfanensis Kom. (Krassn.), which is a folk medicine widely distributed in Xinjiang. As a result, a new coumarin lactone caraganolide A (1) and 35 known components were characterized from the effective extract of C. turfanensis. Furthermore, their anti-neuroinflammatory effects were evaluated in LPS-induced BV2 microglial cells using Griess assay to determine the release of nitric oxide (NO). Compounds 1, 2, 4–6, 9, 13–15, 20, 29 and 30 exhibited significant inhibitory activities and no obvious cytotoxicities were observed at their effective concentrations. It is noteworthy, the new compound caraganolide A (1) (IC50 1.01 ± 1.57 µM) and 3′,7,8-trihydroxy-4′-methoxyisoflavone (5) (IC506.87 ± 2.23 µM) exhibited more excellent action than that of positive control minocycline (IC50 9.07 ± 0.86 μM).Download high-res image (200KB)Download full-size image

The total salvianolic acids are main effective constituents of Salvia miltiorrhiza Bge., a traditional Chinese medicine used for thousands of years. The purpose of present study was to make clear the composition and bioactivities of the minor components of the total salvianolic acids injection. As a result, three new minor phenolic acids (1–3) together with six known compounds (4–9) were characterized from the total salvianolic acids injection. Their structures were elucidated by extensive analysis of the spectral data. The absolute configuration of compounds 1–3 were confirmed by their J7′,8′ observed in 1H NMR spectra, absorption band at approximately 250–260 nm in their CD spectra as well as chemical shifts of C-8″ and C-8‴ displayed in 13C NMR spectra. Then DPPH free radical scavenging assay and NAD(P)H:quinine oxidoreductase 1 (NQO1) inducing activity test were employed to evaluate the antioxidant effect of new minor compounds 1 and 2. Compound 2 showed significant NQO1 inducing activity at 20 μM with IR value 2.6. Meanwhile, DPPH scavenging assay revealed that the inhibition rates of compounds 1 and 2 were 84.3% and 74.9% at 2 mM, respectively.

•Five bioactive benzofuran-chalcanes were characterized from the leaves of Millettia pulchra.•The NQO1 inducing activities of 21 compounds were assayed using Hepa 1c1c7 cell lines.•Six compounds were shown to have potential cancer chemopreventive activity.Five chalcanes ((α′R)-2, α′-dimethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, (α′R, βR)-2′, α′, β-trimethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, (α′S, βR)-2′, α′, β-trimethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, (α′R, βR)-2′, β-dimethoxy-α′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, (α′S, βR)-2′, β-dimethoxy-α′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane) and a flavonoid glycoside (3′, 7-dihydroxy-6-methoxy-4′, 5′-methylenedioxyisoflavone 6-O-β-D- glucopyranoside), together with 15 known components, were isolated from the leaves of Millettia pulchra (Benth) Kurzvar-laxior (Dunn) Z. Wei, a traditional Zhuang medicine. Their chemical structures were established by extensive analysis of NMR, mass spectrometry and ECD spectra. Furthermore compounds (α′R, βR)-2′, β-dimethoxy-α′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, (α′S, βR)-2′, β-dimethoxy-α′-hydroxyethoxy-furano-[4″, 5′′: 3′, 4′] chalcane, quercetin, methyl 2-O-β-D-glucopyranosylbenzoate, 6,7-dimethoxy-3′,4′-methylenedioxyisoflavone and lyoniresinol were suggested to be potential chemopreventive agents because of their significant activity in inducing NQO1 ([NAD(P)H quinine oxidoreductase 1], a phase II metabolism enzyme).NQO1 inducing activities guided phytochemical research led 21 components from the leaves of Millettia pulchra, among them 6 ones might be NQO1 inducers as potential cancer chemopreventive agents.

•Natural QR inducing agents were screened and identified from the hydrolysis products of the total tea seed saponin in Camellia sinensis.•Compounds 7, 12 and 14 were selected as potential QR inducing agents with IR value at 2.87, 3.02 and 2.33.Natural QR (quinine oxidoreductase) inducers play critical roles in cancer chemoprevention. Because tea seed saponins of Camellia sinensis exhibited significant QR inducing activities, this study aimed to find bioactive theasaponin derivatives by structure modification on the sugar part and acyl groups. Three kinds of hydrolysis methods were employed to afford 7 major acid hydrolysis products (1–7), 10 alkaline hydrolysates (8–17) and 2 derivatives (3, 18) by oxidative alkaline-degradation. They were elucidated as kaempferol (1), camelliagenin B (2), camelliagenin A (3), 21-O-angeloybarringtogenol C (4), 5-hydroxymethylfurfural (5), 16-O-angeloybarringtogenol (6), 23-aldehyde-16-O-angeloybarringtogenol (7), desacyl-assamsaponin D (8), desacyl-theasaponin A5 (9), desacyl-assamsaponin E (10), desacyl-theasaponin C1 (11), desacyl-theasaponin E (12), desacyl-theasaponin E13 (13), desacyl-assamsaponin F (14), desacyl-theasaponin F1 (15), desacyl-theasaponin G (16), desacyl-assamsaponin A (17), camelliagenin C (18) accordingly. By the QR inducing activity assay, compounds 7, 12 and 14 were selected as potential QR inducing agents with IR value at 2.87, 3.02 and 2.33.

•Natural flavonoids function as chemopreventive agents from Chinese licorice.•The chemical profile of the effective part was elucidated as 24 flavonoids.•Major components 8, 12 and 20 could be potential NQO1 inducers and tumour angiogenesis inhibitors.Bioactivity guided assay of Gancao showed the flavonoids as being effective in its extract, which contained 24 flavonoids, including isoflavones (1–4), flavanones (5–7), chalcones (8–17), and flavones (18–24). Components 1, 5, 6, 7, 8, 9, 19, 21, and 22 were for the first time identified in licorice. NQO1 and tumour angiogenesis assay suggested three effective flavonoids, α, 4, 2′, 4′ – tetrahydroxydihydrochalcone (8), licochalcone A (12), and licoflavone B (20) as being responsible for the chemopreventive effect. Furthermore, AutoDock 4.2 was employed for molecular docking to clarify the interaction between bioactive flavonoids and NQO1. HPLC analysis was performed to determine the contents of 8, 12 and 20. Therefore the chemical and biological results indicated that flavonoids from the residue of Gancao are promising natural cancer chemopreventive agents.

•Pterostilbene inhibited MAPK signalling pathways and the level of pro-inflammatory mediators in LPS-activated microglia.•The inhibitory effect of pterostilbene on neuroinflammation was confirmed in vivo by using a rat neuroinflammation model.•Pterostilbene possessed neuroprotective anti-inflammatory property that may benefit neurodegenerative diseases.The present study investigated the anti-neuroinflammatory effect of pterostilbene. The data demonstrated that pterostilbene significantly suppresses lipopolysaccharide (LPS)-induced nitric oxide (NO) production and iNOS mRNA expression in BV-2 microglial cells. Pterostilbene significantly inhibits LPS-induced IL-6 and TNF-α production and mRNA expression and the phosphorylation of MAPKs. The effect of pterostilbene on neuroinflammation was further confirmed in vivo using a rat neuroinflammation model. Immunohistochemical study indicated that pterostilbene mitigates LPS-induced microglial activation in rat hippocampal CA1 and dentate gyrus (DG). Pterostilbene significantly inhibits LPS-induced IL-6 and TNF-α mRNA expression in rat hippocampus and their amount in rat serum. This study demonstrated that pterostilbene possesses anti-neuroinflammatory property, suggesting its potential as a dietary supplement that benefits neurodegenerative diseases associated with neuroinflammation.

Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1–29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly.

Neurodegenerative diseases are associated with neuroinflammation, manifested by over-production of nitric oxide (NO) by microglial cells. Now there still lack effective treatment and prevention for the neurodegenerative diseases. Concerning neuroinflammation mediated by microglia cell, bioactivity-guided phytochemical research of Pongamia pinnata (L.) Pierre was performed in this study. A new chlorinated flavonoid, 2′,6′-dichlore-3′, 5′-dimethoxy-[2′′,3′′:7,8]-furanoflavone (1) was identified together with 29 known compounds, including flavonoids (compounds 2–17), isoflavonoids (compounds 18–23), chalcones (compounds 24–25), flavonones (compounds 26–27), triterpenes (28–29) and alkaloid (30) from the effective dichloride methane extract of dry stem of P. pinnata (L.) Pierre. Their structures were elucidated by physicochemical and spectral methods. The anti-neuroinflammatory activities were assayed in BV-2 cells by assessing LPS-induced NO production. Then pongaglabol methyl ether (2), lonchocarpin (24) and glabrachromene II (25) were selected as potential therapeutic agents for neurodegenerative diseases because of their significant anti-neuroinflammatory activities. Furthermore, the characteristics of structure type existing in P. pinnata (L.) Pierre and brief SAR were summarized, respectively.To screen effective natural therapeutic agents for neurodegenerative diseases, 30 effective constituents, including one new chlorinated flavonoid, were identified from dichloride extract of Pongamia pinnata (L.) Pierre. The chalcones (24 and 25) and furanoflavonoid (2) were selected as potential candidate therapeutic agents for neurodegenerative diseases.

Natural NQO1 [NAD(P)H quinine oxidoreductase 1] inducing agents play a critical role in cancer chemoprevention. The expression of NQO1 is regulated by Michael reaction acceptors (MRAs) via the Keap1/Nrf2/ARE signaling pathway. The aims of this study were to identify and characterize novel effective chemopreventive agents from naturally occurring products. Using bioassay-guided isolation approaches 16 bioactive MRAs from Millettia pulchra Kurz var-laxior (Dunn) Z.Wei, also called Yulangsan as a famous Zhuang medicine. The structures were elucidated as chalcone (1–7), flavonone (8–14), flavanone (15) and isoflavan (16). Their electrophilic abilities and NQO1 inducing activity were assessed using GSH (glutathione) rapid screening, and in vitro cell-based (Hepa 1c1c7 cells) assay, respectively. Compounds 3, 4, 6, 13, and 14 showed to have NQO1 inducing activity. Among them, compounds 4 and 14 interact with NQO1 at Gly 149, Gly 150, Phe 106, Typ 105 and His 161, revealed by molecular docking studies.Method for finding out effective chemopreventive agents from Yulangsan using bioactivity-guided identification, bioassay and molecular docking.

Suaeda physophora Pall. is a kind of desert plant mostly growing in saline habitats in Xinjiang Uygur Autonomous Region. In order to have a better utilization of halophytes, a screening for ACE inhibitors from halophytes growing in Xinjiang was carried out. The result showed that the 70% EtOH extract and n-BuOH extract of S. physophora Pall. possessed significant ACE inhibitory activities. So we focused on its biochemical constituents firstly. One new quinazoline alkaloid, namely Suaedine (1), along with six known compounds (2–7) was isolated from the aerial parts of S. physophora Pall. The structure of the new quinazoline alkaloid was established by one- and two-dimensional nuclear magnetic resonance, optical rotation and mass spectrometry analysis. The flavonoid compounds (2–4) and phenolic compound (5) exhibited significant ACE activities. It was the first time to focus on the chemical constituents and bioactivities of this plant.One new quinazoline alkaloid, namely Suaedine (1), along with six known compounds (2–7) was isolated from the aerial parts of S. physophora Pall. The structure of the new quinazoline alkaloid was established by one- and two-dimensional nuclear magnetic resonance and mass spectrometry analysis.Download full-size image

•The transgenic crown galls of Panax quinquefolium broke the α/β unsaturated bond of Licochalcone A.•New alkaloid was produced by the system with the stimulation of Licochalcone A.•The possible biosynthetic pathways were suggested.•The cytotoxicities and NQO1 inducing activities of products were assayed.Licochalcone A, as main constituent of Chinese Gancao (Glycyrrhiza inflate Bat), is responsible for the chemopreventive effect of the herbal. In order to get the bioactive modified molecules of Licochalcone A, it was biotransformed using transgenic crown galls of Panax quinquefolium to afford 9 products including a new alkaloid together with 8 known compounds. Their structures were elucidated by physicochemical and spectral methods as: methyl(12S)-1-[(5-formylfuran-2-yl)methyl]-5-oxopyrrolidine-2-carboxylate (1), methyl(12S)-1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylate (2), 5-hydroxymethyl-2-furfural (3), (S)-methylpyroglutamate (4), 4-hydroxy-2-methoxy-5-(2-methylbut-3-en-2-yl) benzaldehyde (5), 4-hydroxybenzoicacid (6), dibutyl phthalate (7), 3β,6α,12β,25-tetrahydroxy-(20S,24R)-epoxy-dammarane (8), β-sitosterol (9).Among them, compounds 5 and 6 were transformed from Licochalcone A, while 1–4 and 8 were derived from the culture medium stimulated by the substrate. Furthermore, their cancer chemopreventive effect were tested by the assay of NQO1 (NAD(P)H: quinine oxidoreductase 1) inducing activities in Hepa 1c1c cells.To get more derivatives of Licochalcone A and study the ability of the transgenic crown galls of Panax quinquefolium to transform natural chalcone, we modified the structure of Lic.A using transgenic crown galls of P. quinquefolium. Nine products, including one new alkaloid, were elucidated and the possible biosynthetic pathways were suggested. The toxicities and NQO1 inducing activities were assayed.Download full-size image

Ethnopharmacological relevanceDragon׳s blood has been used as a famous traditional medicine since ancient times by many cultures. It is a deep red resin, obtained from more than 20 different species of four distinct genera. Red resin of Dracaena cochinchinensis S.C. Chen, known as Chinese Dragon׳s Blood or Yunnan Dragon׳s Blood, has been shown to promote blood circulation, alleviate inflammation, and to treat stomach ulcers, diarrhea, diabetes, and bleeding. This study investigated an effective approach to identify natural therapeutic agents for neurodegeneration from herbal medicine. The dichloride extract and isolated effective constituents of Chinese Dragon׳s Blood showed quinone oxidoreductase 1 (NQO1) inducing activity and anti-inflammatory effect significantly, which are therapy targets of various neurodegenerative diseases.Materials and methodsMultiple chromatography and spectra analysis were utilized to afford effective constituents. Then Hepa 1c1c7 and BV-2 cells were employed to assay their NQO1 inducing and anti-inflammatory activities, respectively.ResultsBioactivities guided isolation afforded 21 effective constituents, including two new polymers cochinchinenene E (1), cochinchinenene F (2) and a new steroid dracaenol C (16). The main constituent 3 (weight percent 0.2%), 5 (weight percent 0.017%), 4 (weight percent 0.009%), 9 (weight percent 0.094%), 10 (weight percent 0.017%) and 8 (weight percent 0.006%) are responsible for the anti-inflammatory activities of Chinese Dragon׳s Blood. While, new compounds 1, 2 and known compounds 5, 11 showed good NQO1 inducing activities. The brief feature of the activities and structures was discussed accordingly.ConclusionOverviewing the bioactivities and phytochemical study result, 4'-hydroxy-2,4-dimethoxydihydrochalcone (3) and pterostilbene (5) as effective constituents of Chinese Dragon׳s Blood, were found to be potential candidate therapeutic agents for neurodegenerative diseases.To screen the novel natural therapeutic agents for neurodegenerative diseases, 21 effective constituents, including two new polymers (1, 2) and a new steroid (16), were identified from Chinese Dragon’s Blood. The main components 3 and 5 were targeted as potential therapeutic agents of neurodegenerative diseases.Download high-res image (361KB)Download full-size image

Ethnopharmacological relevanceDragon׳s blood has been used as a famous traditional medicine since ancient times by many cultures. It is a deep red resin, obtained from more than 20 different species of four distinct genera. Red resin of Dracaena cochinchinensis S.C. Chen, known as Chinese Dragon׳s Blood or Yunnan Dragon׳s Blood, has been shown to promote blood circulation, alleviate inflammation, and to treat stomach ulcers, diarrhea, diabetes, and bleeding. This study investigated an effective approach to identify natural therapeutic agents for neurodegeneration from herbal medicine. The dichloride extract and isolated effective constituents of Chinese Dragon׳s Blood showed quinone oxidoreductase 1 (NQO1) inducing activity and anti-inflammatory effect significantly, which are therapy targets of various neurodegenerative diseases.Materials and methodsMultiple chromatography and spectra analysis were utilized to afford effective constituents. Then Hepa 1c1c7 and BV-2 cells were employed to assay their NQO1 inducing and anti-inflammatory activities, respectively.ResultsBioactivities guided isolation afforded 21 effective constituents, including two new polymers cochinchinenene E (1), cochinchinenene F (2) and a new steroid dracaenol C (16). The main constituent 3 (weight percent 0.2%), 5 (weight percent 0.017%), 4 (weight percent 0.009%), 9 (weight percent 0.094%), 10 (weight percent 0.017%) and 8 (weight percent 0.006%) are responsible for the anti-inflammatory activities of Chinese Dragon׳s Blood. While, new compounds 1, 2 and known compounds 5, 11 showed good NQO1 inducing activities. The brief feature of the activities and structures was discussed accordingly.ConclusionOverviewing the bioactivities and phytochemical study result, 4'-hydroxy-2,4-dimethoxydihydrochalcone (3) and pterostilbene (5) as effective constituents of Chinese Dragon׳s Blood, were found to be potential candidate therapeutic agents for neurodegenerative diseases.To screen the novel natural therapeutic agents for neurodegenerative diseases, 21 effective constituents, including two new polymers (1, 2) and a new steroid (16), were identified from Chinese Dragon’s Blood. The main components 3 and 5 were targeted as potential therapeutic agents of neurodegenerative diseases.Download high-res image (361KB)Download full-size image

•Isofraxetin-6-O-β-d-glucopyranoside was deglycosylated using Angelica sinensis (Oliv.) Diels callus.•A new coumarin was produced by the system with the stimulation of isofraxetin-6-O-β-d-glucopyranoside.•Anti-inflammatory effects of transformed products were evaluated, and possible biosynthetic pathways were described.Isofraxetin-6-O-β-d-glucopyranoside, identified from traditional medicinal herbal Xanthoceras sorbifolia Bunge, has been demonstrated to be a natural neuroinflammatory inhibitor. In order to obtain more derivatives with potential anti-neuroinflammatory effects, biotransformation was carried out. According to the characteristics of coumarin skeleton, suspension cultures of Angelica sinensis (Oliv.) Diels callus (A. sinensis callus) were employed because of the presence of diverse phenylpropanoids biosynthetic enzymes. As a result, 15 products were yielded from the suspension cultures, including a new coumarin: 8′-dehydroxymethyl cleomiscosin A (1), together with 14 known compounds. Their structures were elucidated by extensive spectroscopic analysis. Furthermore, the biotransformed pathways were discussed. Among them, compound 13 was transformed from isofraxetin-6-O-β-d-glucopyranoside, while compounds 1–6, 10–12, 14–15 were derived from the culture medium stimulated by the substrate. The biotransformation processes include hydroxylation, oxidation and esterification. Furthermore, their inhibitory effects on lipopolysaccharide (LPS)-activated nitric oxide (NO) production were evaluated in BV2 microglial cells. It is worth noting that, 1, 1′-methanediylbis(4-methoxybenzene) (3), obtucarbamates A (5), 2-nonyl-4-hydroxyquinoline N-oxide (10) and 1H-indole-3-carbaldehyde (11) exhibited significant inhibitory effect against neuroinflammation with IC50 values at 1.22, 10.57, 1.02 and 0.76 μM respectively, much stronger than that of the positive control minocycline (IC50 35.82 μM).

•The anti-neuroinflammatory material basis of A. sparsifolia Shap. was clarified.•SAR between the constituents and anti-neuroinflammatory activities was discussed.•Compounds 16 and 33 were suggested to be potential neuroinflammation inhibitors.Neuroinflammation is a key contributor to neuronal damage in neurodegenerative diseases. In our previous work on natural effective neuroinflammatory inhibitors, Alhagi sparsifolia Shap. (Leguminosae), a folk medicine widely distributed in Xinjiang, attracted our attention because of its significant anti-neuroinflammatory effect. Therefore, further investigation of the bioactive material basis was carried out. As a result, 33 major components were characterized and identified by chromatographic and spectral methods, respectively. Furthermore, the anti-neuroinflammatory effects of the extract and purified constituents were evaluated in LPS-induced N9 cells in vitro. The results displayed that compounds 1, 2, 3, 5, 6, 8, 11, 15, 16, 17, 22, 23, 25, 26, 28, 30, 33 could exhibit significant inhibitory activities without obvious cytotoxicities at their effective concentrations. Especially, isorhamnetin (1) (IC50 17.87 μM), quercetin (2) (10.22 μM), 3′,7-dihydroxyl-4′-methoxylisoflavone (5) (17.43 μM), 3′,7-dihydroxyl-4′,6-dimethoxylisoflavone (6) (11.21 μM), syringgaresinol (16) (2.68 μM), bombasinol A (17) (7.61 μM), aurantiamide (23) (14.91 μM) and 1,3,3,4-tetramethyl cyclopentene (33) (2.63 μM) showed much stronger inhibiting effect than that of the positive control minocycline (19.89 μM). Therefore, the effective compositions might be responsible for the significant neuroinflammation inhibitory activities exhibited by the herb. Moreover, compounds 16 and 33 could be good leading compounds for the development of potential therapeutic agents against neurodegenerative diseases.