Introduction
Review methodology
Plant sources of DBCLS and their phytochemical profile, traditional uses and current medical applications
Schisandra chinensis
Species | Part of plant | Group of compounds | Chemical compounds | References |
---|---|---|---|---|
Schisandra chinensis | Fruits | DBCLS | Schisandrin, schisandrins B, C, γ-schisandrin, schisantherins A, B, schisanthenol, deoxyschisandrin, gomisin A, G, schisanchinins A–D, nicotinoylgomisin | |
Dibenzylbutane lignans | Schineolignans A–C | |||
Tetrahydrofuran lignans | Schinlignin A, B | |||
Triterpenoids | Schisanartanin A, B, schisanartanin A, B, 3,4-seco-21,26-olido-artan acid triterpenoid-wuweizilactone | |||
Bisnortriterpenoids | Wuweizidilactone | [34] | ||
Bioelements | Co, Mg, Fe, Zn, Cr, Ni, Cu, Ca, Mg, Fe, Mn, B | |||
Leaves and stems | Triterpenoids | Schinchinenins A–H, schinchinenlactones A–C | [41] | |
Nortriterpenoids | Schinesdilactone A. B, isoschicagenin C, schicagenins A–C, schisdilactones A–G | |||
DBCLS | Schisandrin, gomisin A, J, pregomisin, angeloylgomisin H, Q | [43] | ||
Leaves | DBCLS | Deoxyschisandrin, schisandrin B, gomisin G, A, schisantherin, schisandrin | ||
Flavonoids | Isoquercitrin, hyperoside, rutin, myricetin, quercetin, quercetin and kaempferol glycosides: ( +)-isoscoparin, quercetin 3-o-β-l-rhamnopyranosyl (1 → 6)-β-d glucopyranoside | [49] | ||
Phenolic acids | Chlorogenic, p-coumaric, p-hydroxybenzoic, protocatechuic, salicylic, syringic, gentisic, ferulic, cinnamic acids | [49] | ||
Schisandra sphenanthera | Fruits | DBCLS | Pregomisin, gomisin C, S, K3, J, U, epigomisin O, 6-o-benzoylgomisin, benzoylgomisin U, methylgomisin, tigloylgomisin P, angeloylgomisin P | [63] |
Derivatives of DBCLS | Schisfenins C–G, schisfenone | |||
4-Aryltetralin lignan | Schisandrone | |||
Aryltetralone lignan | Schisphentetralone A | |||
3-Dimethyl-1,4-diarylbutane lignans | d, l-Anwulignan, sphenanlignan | |||
2,5-Diaryltetrahydrofuran lignans | Chicanin, d-epigalbacin, ganschisandrine | |||
Triterpenoids | Schisandronic acid (ganvuweisic acid), anvuweisic acid, kadsuric acid, coccinic acid, schinalactones A–C, G, schisanol | |||
Nortriterpenoids | Sphenalactones A–D, sphenadilactone C, sphenazine | |||
Stems | DBCLS | Gomisin B, G, O, epigomisin O, schisantherin A, D, marlignan E, angeloylgomysin Q, schisfenlignans A–D | [67] | |
Roots | Terahydrofuran lignans | Schiglaucin A, B, epoxyzuonin, thalaumidine, myristartenol A | [68] | |
Schisandra henryi | Leaves and stems | DBCLS | Gomisin G, schisantherin A, benzylgomisin Q, deoxyschisandrin, schisandrin | |
Aryltetraline lignans | Wulignan A1, A2, epiwulignan A1, enshicine, epienshicine, dimethylwulignan A1 | |||
Dibenzylbutane lignans | Henricin A, B, isoanwulignan | |||
Tetrahydrofuran lignan | Ganschisandrine | [80] | ||
Stems | Triterpenoids | Henrisquinines A–C, acids: isoschisandronic, kadsuric, anwuweizic, schisandronic, nigranic, 3-ethyl ester of nigranic acid, schisanlactone B | [81] | |
Nortriterpenoids | Henridilactones A-D, schiprolactone A | [82] | ||
Fruits | DBCLS | Schisantherin B, schisanhenol, schisanhenrin | [83] | |
Terpenoids acids | Kadsuric acid, schisanhenric acid | [83] | ||
Leaves | DBCLS | Schisandrin, gomisin G, schisantherin A, B, deoxyschisandrin, schisandrin C, | [77] | |
Phenolic acids | Gallic, neochlorogenic, kaftaric, caffeic acids | [77] | ||
Flavonoids | Hyperoside, rutin, trifolin, quercitrin, quercitin and kaempferol | [77] | ||
Schisandra rubriflora | Fruits | DBCLS | Angeloylgomisin P, Q, benzoylgomisin Q, deoxyschisandrin, epiwulignan A1, isogomisin O, rubrilignans A, B, rubrischisantherin | [88] |
Phenolic acids | Chlorogenic acid, cryptochlorogenic acid | [89] | ||
Flavonoids | Hyperoside, rutin, isoquercitrin, guaijaverin, trifolin, quercetin, kaempferol, isorhamnetin | [89] | ||
Leaves | Dibenzylbutane lignans | Mesomono-methyl-dihydroguaretic acid, mesodihydroguaretic acid, 4,4′-(2R,3S)-2,3-dimethylbutane-1,4-diyl)bis(1,2-dimethoxybenzene) | [86] | |
Arylnaphthalene lignans | (8R,7′R,8R)-5-Hydroxy-4,3′,4′-trimethoxy-2,7′-cyclolignan | [86] | ||
Flavonoids | Hyperoside, rutin, isoquercetin, guaijaverin, trifolin, quercetin, kaempferol, isorhamnetin | [88] | ||
Stems | DBCLS | Angeloylgomisin Q and P, schisandrin, schisantherin A, gomisin D, epigomisin O, tiglomisin P, benzoylgomisin Q, machilin D, rubrisandrin A, B, schirubrins A–D | [86] | |
Megastiman glycosides | Megastigmano-3-α-4β-9ξ-triol-3-o-β-d-glucopyranoside and 7-megastigmano-3-ol-9-one-3-o-α-l-arabifuranosyl-(1 → 6)–β–d-glucopyranoside | [87] | ||
Phenolic acids | Syringic, neochlorogenic, chlorogenic, cryptochlorogenic acids | |||
Flavonoids | Naringin, didimine, mazopsin 6-o-glucopyranoside, hyperoside, rutine, isoquercetin, guaijaverin, trifolin, quercetin, kaempferol, isorhamnetin | |||
Bisnortriterpenoids | Rubriflordilactones A, B | |||
Stems and leaves | Nortriterpenoids | Rubriflorins A–J | ||
Schisandra grandiflora | Fruits | DBCLS | Gomisins A, B, D, K3, M1 and N, deoxyschisandrin, schisandrin, (–) gomisin K1, epigomisin O, tiglomisin P, benzoylgomisin O, schisandrin C | |
Tetrahydrofuran lignans | Chicanine | |||
Derivatives of tetrahydrofuran lignans | Veraguensin | |||
Dibenzylbutane lignans | Macelignan | |||
Diaryldimethylbutane lignans | Saurulignan B | |||
Tetralin lignans | Arisantetralone C. D | |||
Triterpenoids | Schisandronic acid, schizandrolic acid | |||
Sesquiterpenoids | Viddaranal A–C, isokuparenal, schisanspheninal A, vidarol peroxide | [96] | ||
Leaves and stems | Nortriterpenoids | Schigrandilactones A–C, lancifodilactones C, D, 11K, L, N, 12 microrandilactones A,2, henridilactones A, B | [100] | |
Stems | Triterpenoids | Granditriol, 2α,3β,23-trihydroxyurs-12,20(30)-dien-28-oic acid β-d-glucopyranosyl ester, acetylursolic acid, ursolic acid, 2α,3α-dihydroxyurs-12-ene-28-oic acid, corosolic acid, asiatic acid, 2α,3α,19α-trihydroxyurs-12-ene-28-oic acid, 2α,3α,23-trihydroxyurs-12-ene -28-oic acid, 23-hydroxyursolic acid, maslinic acid, 2α,3β,23-trihydroxyolean-12-en-28-oic acid β-d-glucopyranosyl ester, lupeol, betulinic acid | [101] | |
Schisandra propinqua | Stems | DBCLS | Interioterin A, benzoylgomisin O, gomisin G, O schisantherin, heteroclithin A, tigloylgomisin P, angeloylgomisin O, angeloylisogomisin O, cadsulignan L(4), ( ±) 5,8-epoxy-6,7-dimethyl-2′,3′,2″,3″-dimethylenedioxy-4′,1″-dimethyl-1,2:3,4-dibenzo-1,3-cyclooctadiene, wuweizisu C, angeloyl-( +)-gomisin K, methylisogomisin O, isogomisin O, angeloylisogomisin O, angeloygomisin O, benzoylgomisin O, epigomisin O, propinvanins A–D | |
Neolignans | 4,4-Di(4-hydroxy-3-methoxyphenyl)-2,3-dimethylbutanol | [132] | ||
Derivatives of lignans | Galgravin, veraguensin, octadecanoic acid 2,3-dihydroxypropyl ester, 2-hexadecanoic acid 3-dihydroxypropyl ester, tetracosanoic acid 2,3-dihydroxypropyl ester | [102] | ||
Triterpenoids acids | Schisandrolic, isoschisandrolic, nigranic, manvuweic, schisandronic acids | [118] | ||
Nortiterpenoids | Propindilactones E-J | [110] | ||
Stems and leaves | Triterpenoids | Propindilactone T, U, changnanic acid 3-methyl ester, schipropine acid | [136] | |
Leaves | Nitrophenol glycosides | 6′-o-Alpha-l-arabinofuranosylthalictoside, 6′-o-beta-d-apiofuranosylthalictoside, talictoside, icarizide D2, prinsepiol, ( +)-1-hydroxypinoresinol, ( +)-medioresinol | [112] |
Schisandra sphenanthera
Schisandra henryi
Schisandra rubriflora
Schisandra grandiflora
Schisandra propinqua
Schisandra glabra
Chemical structure of DBCLS
Pharmacokinetics and bioavailability of DBCLS
Current preclinical evidence on anticancer molecular mechanisms of DBCLS
Apoptosis induction
Anticancer mechanism | Molecular and cellular target | Tested DBCL | Experimental model | Dosage | Anticancer effect | Refs. |
---|---|---|---|---|---|---|
Apoptosis induction | Mitochondrial apoptotic pathway (Cytochrome c, Caspases) | Schisandrin B | Human gallbladder cancer GBC-SD and NOZ cell lines | Schisandrin B at 0, 30, 60 and 90 μmol/L | ↓ Cell viability ↑ Apoptosis | [129] |
Cell cycle arrest | G0/G1, G1/S, G2/M phases | Schisandrin B | Gastric cancer SGC-7901 cell line | Schisandrin B (75 μM), or apatinb (60 μM) with schisandrin B (75 μM) | ↓ Cell proliferation ↓Invasion, ↓Migration ↑Efficacy of apatinib | [132] |
Gomisin A | Cervical cancer HeLa cell line Mice C57BL/6 (in vivo) mouse melanoma B16F10 cell line and human melanoma cell line A375SM (in vitro) | Gomisin A at 10, 30 and 100 µM in the presence or absence of TNF-α (20 ng/mL) gomisin A at 2, 10, and 50 mg/kg orally administered to mice once a day, mice were sacrificed after 14 days; gomisin A at 0, 25, 50, 100 µM gomisin A; for 24 h | ↓ Cell viability ↓ Migration and invasion | |||
Schisantherin A | Human tongue squamous HN4 cell line, macrophage-like RAW264.7 cell line, human gastric MKN45 and SGC-7901 cancer cell lines, human breast cancer MCF7 and MDA-MB-231 cell lines | Schisantherin A at 0 nM, 500 nM, 1 μM and 2.5 μM | ↑ Anti-proliferative effect ↑ Cell cycle arrest | [134] | ||
ROS generation | Oxidative stress response | Gomisin L1 | Ovarian cancer A2780 and SKOV3 cell lines (in vitro) | Gomsin L1 at 3.12, 6.25, 12.5, 25, 50 and 100 µM | ↑ Apoptosis via ROS production | [130] |
Autophagy induction | mTOR | Gomisin J | Breast cancer MCF7 and MDA-MB-231, and normal MCF10A cell lines (in vitro) | Gomisin J at 10–30 µg/mL | ↑ Autophagy-mediated cell death | [131] |
Inhibition of proliferation, invasion, metastasis | MMP activity modulation | Schisandrin B | Prostate cancer DU145 and LNCaP cell lines (in vitro) | Schisandrin B at 0, 50, 100, 150 and 200 µM | ↓ Cell growth ↓ Migration ↑ Invasion ↑ Apoptosis | [135] |
Chemotherapy resistance modulation | Sensitization to chemotherapy agents, P-glycoprotein expression | Schisandrin B | Breast cancer MDA-MB-435S, MCF-7/ADR, MCF-7 and ovarian cancer A2780 cell lines (in vitro) | Schisandrin B at 10 μM | ↑ Sensitivity to doxorubicin ↑ Apoptosis ↓ Tumor growth and migration | |
Cervical cancer (Caski cells) BALB/c nude mice xenografts (in vitro and in vivo) | In vivo experiments Schisandrin B at 20 mg/kg b.w | ↓ Cell viability ↓ Colony formation ↑ Apoptosis ↓ Tumor cell invasion ↑ Cytotoxic effect of docetaxel | [142] | |||
Schisandrin B combined with epirubicin | Breast cancer MDA-MB-435S, MCF-7/ADR, MCF-7 and ovarian cancer A2780 cell lines (in vitro) | Schisandrin B at 10 μM | ↑ Cytotoxic effect ↓ Vascular mimicry | [137] | ||
Schisandrin B | Gastric cancer SGC7901 and BGC823 cell lines (in vitro) | Schisandrin B at 0, 10, 25, 50, 100, 200 μM | ↑ Cytotoxic effect by arresting G0/G1 cell cycle | [138] | ||
Schisandrin B | Gastric cancer SGC-7901 cell line (in vitro) | Schisandrin B at 75 µM | ↑ Invasion and migration of apatinib ↑ Cytotoxic drug-induced apoptosis | [132] | ||
Schisandrin B | Gastric cancer BGC-823 cell line (in vitro) and nude mouse model bearing allograft (in vivo) | Schisandrin B at 0.1 μM (in vitro), 5 mg/kg b.w. (in vivo) | ↓ Tumor metastasis; Selective accumulation at tumor site | [140] | ||
Regulation of signaling pathways | MAPK, PI3K/Akt, NF-κB, Wnt/β-catenin | Schisandrin B | Prostate cancer DU145 and LNCaP cell lines (in vitro) | Schisandrin B at 0, 50, 100, 150 and 200 µM | ↓ Cell proliferation; ↑ Apoptosis | |
Gomisin G | Breast cancer MDA-MB-231 and MDA-MB-468 cell lines (in vitro) | Gomisin G at 1, 5 and 10 µM |
Autophagy induction
Cell cycle arrest
Inhibition of cancer cell proliferation, invasion and metastasis
Chemotherapy resistance modulation
Regulation of signaling pathways
DBCLS as potential chemotherapeutic adjuvants
Bicyclol: therapeutic effects and anticancer potential
Wuzhi capsules and their role in enhancing chemotherapy
Study Focus | Tested compound/ Drug | Methodology | Major Findings | References |
---|---|---|---|---|
Hepatoprotective effects | Bicyclol | Inhibition of hepatocyte apoptosis | No noticeable side effects Increases hepatic heat shock proteins | |
Anticancer activity on HepG2 cells | Cell cycle inhibition autophagy initiation | Inhibits HepG2 cell proliferation, Decreases levels of several key proteins involved in cell cycle and proliferation | [151] | |
Anticancer activity on renal cancer/carcinoma cell | Apoptosis initiation Cell cycle arrest | Increases oxidative stress in cancer cells | [152] | |
Hepatocellular carcinoma | Mice model | Significant reduction in liver tumors; 100% hepatoma and 50% hepatocellular carcinoma in control group | [153] | |
Hepatoprotective and anticancer | ICR mice model with cisplatin | Reduces cisplatin-induced liver tissue damage. Enhances liver enzymes | [154] | |
Multidrug resistance | In vitro studies | Reduces resistance to vincristine and adriamycin in cancer cell lines | [155] | |
Anti-transformative effects | Inhibition of WB-F344 cell transformation | Inhibits malignant transformation of cells | [151] | |
Combination therapies | Wuzhi capsules | Co-administered with methotrexate | Affects Methotrexate pharmacokinetics, suggesting potential to reduce inflammation in immunosuppressive therapies | [152] |
Nephrotoxic and hepatotoxic effects | Co-administered with cyclophosphamide | Potentially attenuates side effects of cyclophosphamide Alters pharmacokinetics to increase drug efficacy | [153] | |
Drug interactions | Co-administered with cyclosporine A, paclitaxel, tacrolimus | Affects blood levels of administered drugs May influence absorption and first-pass metabolism, increasing the oral bioavailability of tacrolimus |