Protection of Skin Fibroblasts from Infrared-A-Induced Photo-Damage Using Ginsenoside Rg3(S)-Incorporated Soybean Lecithin Liposomes.

Protection of skin cells from chronic infrared-A (IRA) irradiation is crucial for anti-photoaging of the skin. In this study, we investigated the protective activity of Rg3(S) and Rg3(S)-incorporated anionic soybean lecithin liposomes (Rg3/Lipo) with a size of approximately 150 nm against IRA-induced photodamage in human fibroblasts. The formulated Rg3/Lipo showed increased solubility in aqueous solution up to a concentration of 200 µg/ml, compared to free Rg3(S). In addition, Rg3/Lipo exhibited superior colloidal stability in aqueous solutions and biocompatibility for normal human dermal fibroblasts (NHDFs). After repeated IRA irradiation on NHDFs, elevated levels of cellular and mitochondrial reactive oxygen species (ROS) were greatly reduced by Rg3(S) and Rg3/Lipo. In addition, cells treated with Rg3/Lipo exhibited noticeably reduced apoptotic signals following IRA irradiation compared to untreated cells. Thus, considering aqueous solubility and cellular responses, Rg3/Lipo could serve as a promising infrared protector for healthy aging of skin cells.

Different Associations of Coffee Consumption with the Risk of Incident Metabolic Dysfunction-Associated Steatotic Liver Disease and Advanced Liver Fibrosis.

Although coffee has a potential hepatoprotective effect, evidence of the relationship between coffee consumption and metabolic dysfunction-associated steatotic liver disease (MASLD) remains conflicting. There is limited evidence regarding the most appropriate coffee intake to prevent advanced liver fibrosis (ALF) in patients with MASLD. We investigated the effect of coffee consumption on MASLD and ALF among 5266 participants without MASLD and 1326 with MASLD but without ALF. Participants were grouped by coffee intake: non-consumers, >0 and <1 cups/day, ≥1 and <2 cups/day, and ≥2 cups/day. Over a median follow-up of 11.6 years for MASLD and 15.7 years for ALF, coffee consumption did not significantly affect the incidence of MASLD, with 2298 new cases observed. However, a notable inverse association was found with ALF risk in patients with MASLD among those consuming coffee ≥2 cups/day (adjusted HR 0.57, 95% CI: 0.37-0.90, p = 0.014), especially among those consuming coffee ≥2 and <3 cups/day (adjusted HR 0.51, 95% CI: 0.30-0.89, p = 0.018). This suggests a potential hepatoprotective effect of coffee, especially in preventing the progression of liver fibrosis in patients with MASLD. These findings propose that coffee consumption could be a simple and effective approach to mitigate the risk of ALF in individuals with MASLD.

Effects of electroacupuncture on apoptotic pathways in a rat model of focal cerebral ischemia.

In this study, we investigated the molecular mechanisms underlying the anti-apoptotic properties of electroacupuncture (EA) in a rat model of middle cerebral artery occlusion (MCAO). Treatment with 2 Hz EA (1 mA) resulted in a markedly reduced infarct area after stroke, particularly in the middle region of the brain. Treatment with EA resulted in a significant decrease in the number of apoptotic cells identified by Hoechst 33342 and TUNEL staining. According to the results of the analysis for proteins involved in apoptosis, treatment with EA resulted in a significantly reduced expression of death receptor (DR)5. Among the members of the Bcl­2 family, a higher expression of anti-apoptotic Bcl­2 and Bcl­xL was observed in the rats treated with EA, compared with the untreated rats with MCAO. As regards the expression of the inhibitor of apoptosis protein (IAP) family, a higher expression of anti-apoptotic cIAP­1 and ­2 was also detected in the cortex of the EA­treated rats. Using western blot analysis, we observed that activated caspase­3 was only significantly arrested by EA treatment in the rats with MCAO; however, according to the results of the caspase assay, the activities of caspase­3, ­8 and ­9 were markedly inhibited by EA treatment. These results suggest that treatment with EA exerts anti­apoptotic effects in cerebral ischemia in a rat model of MCAO and that these effects are associated with the inhibition of the DR and mitochondrial apoptotic pathways.

Effects of electroacupuncture on spinal α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor in rats injected with complete Freund's adjuvant.

The effects of electroacupuncture (EA) on spinal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunits in male rats injected with complete Freund's adjuvant (CFA) were investigated. Bilateral EA stimulation (2 Hz, 1 mA) was administered by needle insertion for 30 min once daily at acupoints corresponding to Zusanli and Sanyinjiao, and the thermal thresholds were measured. To examine the changes in the AMPA receptor subunits, the L4-5 segments of the spinal cord were analyzed by qPCR, western blot analysis and immunohistochemistry. The CFA-induced thermal sensitivity of the rat hind paw was significantly inhibited by EA stimulation from day 3 following CFA injection. On day 5 following CFA injection, there were no significant changes in the expression of the AMPA receptor GluR1 subunit in the CFA-injected rats with or without EA stimulation, compared with the control rats. However, the expression of the GluR2 subunit was significantly decreased by CFA treatment. Western blot analysis revealed that the expression of the phosphorylated GluR1 subunit in the control rats was not significantly different compared with that in the CFA-injected rats with and without EA stimulation. However, phosphorylation of the ipsilateral GluR2 subunit was significantly increased in the CFA-injected rats, and this activation was prevented by EA stimulation. Immunohistochemical analysis revealed a greater expression of phospho-GluR2 following CFA injection, which was inhibited by EA stimulation. These results suggested that phosphorylation of the AMPA receptor, particularly the GluR2 subunit, may be important in EA analgesia of CFA-induced inflammation.

Ethanol extract of Cnidium officinale exhibits anti-inflammatory effects in BV2 microglial cells by suppressing NF-κB nuclear translocation and the activation of the PI3K/Akt signaling pathway.

Chronic microglial activation endangers neuronal survival through the release of various toxic pro-inflammatory molecules; thus, negative regulators of microglial activation have been identified as potential therapeutic candidates for several neurological diseases. In this study, we investigated the inhibitory effects of an ethanol extract of Cnidium officinale rhizomes (EECO), which has been used as a herbal drug in Oriental medicine, on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), as well as that of pro-inflammatory cytokines in BV2 microglia cells. EECO significantly inhibited the excess production of NO and PGE2 in LPS-stimulated BV2 microglia cells. It also attenuated the expression of inducible NO synthase, cyclooxygenase-2, as well as that of pro-inflammatory cytokines, such as interleukin-1ß and tumor necrosis factor-α. Moreover, EECO exhibited anti-inflammatory properties by suppressing nuclear factor-κB (NF-κB) translocation and the activation of the phosphoinositide 3-kinase/Akt pathway in LPS-stimulated BV2 cells. These results indicate that EECO exerts anti-inflammatory effects in LPS-stimulated BV2 microglial cells by inhibiting pro-inflammatory mediators and cytokine production by blocking the NF-κB pathway. These findings suggest that EECO has substantial therapeutic potential for the treatment of neurodegenerative diseases accompanied by microglial activation.

Hexane extract from Polygonum multiflorum attenuates glutamate-induced apoptosis in primary cultured cortical neurons.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum has traditionally had wide use as an anti-aging treatment in East Asian countries. We investigated the neuroprotective effects of Polygonum multiflorum against glutamate-induced neurotoxicity with a focus on the anti-apoptotic mechanism in primary cultured cortical neurons. MATERIAL AND METHODS: Cell viability, cytotoxicity, morphological, flow cytometry, Western blot, and caspase activity assays were performed for examination of the neuroprotective effects of active hexane extract from Polygonum multiflorum (HEPM). RESULTS: Pretreatment with HEPM resulted in significantly decreased glutamate-induced neurotoxicity in a concentration-dependent manner and also resulted in drastically inhibited glutamate-induced apoptosis. Treatment with HEPM resulted in decreased expression of glutamate-induced death receptor (DR)4, and enhanced expression of glutamate-attenuated anti-apoptotic proteins, including Bcl-2, XIAP, and cIAP-1, and slightly reduced glutamate-induced cleavage of Bid. In addition, treatment with HEPM resulted in suppressed glutamate-induced activation of caspase-8, caspase-9, and caspase-3, and, subsequently, decreased degradation of poly(ADP-ribose) polymerase, ß-catenin, and phospholipase Cγ1 protein, which are downstream targets of activated caspase-3. CONCLUSIONS: The results of this study demonstrated that HEPM exerts a neuroprotective effect against glutamate-induced neurotoxicity via inhibition of apoptosis. This protection may be mediated through suppression of DR4 and up-regulation of Bcl-2, XIAP, and cIAP-1, as well as inhibition of caspase activation, resulting in prevention of apoptosis of cortical neurons.

Partially purified Asiasari radix inhibits melanogenesis through extracellular signal-regulated kinase signaling in B16F10 cells.

The active fraction of the extract of Asiasari radix, the 60% methanol chromatographic fraction from the ethyl acetate layer (PPAR), was used to investigate the melanogenesis signal pathway in B16F10 melanoma cells. PPAR led to significantly decreased melanin synthesis and tyrosinase activity in a dose-dependent manner. PPAR also reduced the expression of melanogenesis-related proteins including microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein (TRP)s while down-regulating the expression of mRNA of MITF and tyrosinase. Melanogenesis-regulating signals, such as mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt and p38 mitogen-activated protein kinase (MAPK) were evaluated, and ERK was activated by PPAR. The selective inhibitor of MEK/ERK, PD98059, abrogated all suppressive activities of PPAR on melanin biosynthesis, tyrosinase activation and expression of melanogenesis-related proteins. These results suggest that ERK activation by PPAR contributes to reduced melanin synthesis via ERK signal pathway-mediated suppression of MITF and its downstream signal pathway.

Involvement of intracellular calcium on the phosphorylation of spinal N-methyl-D-aspartate receptor following electroacupuncture stimulation in rats.

This study examined the role of the intracellular calcium chelator, bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA), in modulating the phosphorylation of the spinal N-methyl-d-aspartate receptor (NMDAR) NR1 and NR2B subunits after 2Hz electroacupuncture (EA) in rats. The level of EA analgesia was reduced by an intraperitoneal injection of BAPTA at a higher dose after terminating EA stimulation. At 60min after the EA treatment, the total number of c-fos-immunolabeled neurons in each region of the dorsal horn in lumbar segments (L4-5) was decreased by the BAPTA injection, particularly in the Nucleus proprius. The BAPTA injection decreased significantly the mean integrated optical density of phosphorylated NR1 subunit in the superficial laminae and neck region, and the phosphorylated NR2B subunit in the superficial laminae. Western blot analyses confirmed decreased levels of both phosphorylated subunits. In conclusion, intracellular calcium may play an important role in low-frequency EA analgesia by modulating the phosphorylation state of the spinal NMDAR subunits.

Partially purified Curcuma longa inhibits alpha-melanocyte-stimulating hormone-stimulated melanogenesis through extracellular signal-regulated kinase or Akt activation-mediated signalling in B16F10 cells.

Bioassay-guided fractionation of Curcuma longa by solvent partitioning and purification with octadecylsilane open column chromatography yielded a partial purification. The active 80% methanol chromatographic fraction from the ethyl acetate layer [partial purification from C. longa (PPC)] was used to investigate the alpha-melanocyte-stimulating hormone (alpha-MSH)-stimulated melanogenesis signal pathway in B16F10 cells. In cells stimulated alpha-MSH, PPC inhibited cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related proteins (TRP). Melanogenesis-regulating signalling such as mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt was activated by PPC in alpha-MSH-stimulated B16F10 cells. The suppressive activity of PPC on alpha-MSH-induced melanogenesis was abrogated by selective inhibition of MEK/ERK (PD98059) and PI3K (LY294002). MEK/ERK or Akt activation by PPC may contribute to reduced melanin synthesis via MITF and its downstream signal pathway including tyrosinase and TRPs in alpha-MSH-induced melanogenesis.

Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells.

Cimicifuga rhizoma has long been used in traditional Korean medicine. In particular, a Cimicifuga heracleifolia extract (CHE) was reported to inhibit the formation of glutamate and the glutamate dehydrogenase activity in cultured rat islet. Glutamate activates melanogenesis by activating tyrosinase. Accordingly, it was hypothesized that a CHE might inhibit the melanogenesis-related signal pathways including the inhibition of microphthalmia-associated transcription factor (MITF)-tyrosinase signaling and/or the activation of extracellular signal-regulated kinase (ERK)-Akt signaling. The results showed that CHE inhibits the cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including MITF, tyrosinase and tyrosinase-related protein (TRP)s in alpha-melanocyte-stimulating hormone-stimulated B16 cells. Moreover, CHE phosphorylates MEK, ERK1/2 and Akt, which are melanogenesis inhibitory proteins. The data suggest that CHE inhibits melanogenesis signaling by both inhibiting the tyrosinase directly and activating the MEK-ERK or Akt signal pathways-mediated suppression of MITF and its downstream signal pathway, including tyrosinase and TRPs. Therefore, C. heracleifolia would be a useful therapeutic agent for treating hyperpigmentation and an effective component in whitening and/or lightening cosmetics.

Effects of protein phosphatase inhibitors on the phosphorylation of spinal cord N-methyl-D-aspartate receptors following electroacupuncture stimulation in rats.

The present study investigated the role of inhibitor of protein phosphatases 1 and 2A on the modulation of the phosphorylation of the spinal N-methyl-D-aspartate receptor (NMDAR) NR1 and NR2B subunits following electroacupuncture (EA) stimulation in rats. Bilateral 2Hz EA stimulations with 1.0 mA were delivered at those acupoints corresponding to Zusanli and Sanyinjiao to men via needles for 30 min. EA analgesia was slightly reduced by the intrathecal injection of calyculin A during EA stimulation. At 60 min after the termination of EA stimulation, the levels of c-fos, serine phosphorylation of NR1 and NR2B by Western analysis had increased in the L(4-5) segments of the spinal cord after EA treatment. These expressions were enhanced by the intrathecal injection of calyculin A and immunohistochemical analyses confirmed the significant increase of these proteins. As for the regional reaction of NMDAR subunits, a mean integrated optical density of phosphorylated NR1 and NR2B subunits was potentiated by calyculin A injections in the superficial laminae and neck region and superficial laminae and nucleus proprius, respectively. It can be concluded that protein phosphatase may play an important role in EA analgesia by modulating the phosphorylation state of spinal NMDAR subunits.

Electroacupuncture inhibits inflammatory edema and hyperalgesia through regulation of cyclooxygenase synthesis in both peripheral and central nociceptive sites.

We investigated the anti-inflammatory effects of electroacupuncture (EA) on carrageenan-induced inflammatory model in association with peripheral and spinal COX-2 expression. EA with 2, 15 and 120 Hz, especially 2 Hz, had significant inhibitory effects on the developing of edema and hyperalgesia, which was measured in 30-min intervals after carrageenan injection. Therefore, we investigated whether the effect of 2 Hz EA on carrageenan-induced edema and hyperalgesia is associated with peripheral and spinal expression of inflammatory proteins. The expression of cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) was inhibited by 2 Hz EA in carrageenan-injected rat paws. Interestingly, we found that the mRNA of COX-1 and COX-2 expression in the spine was not induced by 2 Hz EA treatment after carrageenan-induced peripheral inflammation. In addition, synthesis of prostaglandin E(2) (PGE(2)) was partially inhibited by 2 Hz EA treatment in both peripheral and spinal nociceptive regions. In conclusion, EA treatment might be a useful therapy for mitigation of inflammatory edema and hyperalgesia through regulation of COX-2 expression in both peripheral and central nociceptive sites.

Effects of mycelial culture of Phellinus linteus on ethanol-induced gastric ulcer in rats.

The gastroprotective effects of a mycelial culture of Phellinus linteus (MCPL) were evaluated by determining the ulcer index, gastric mucus content, histopathological observation and histochemical properties of mucin in an ethanol-induced ulcer model of rats. Preadministration with MCPL at doses of 20 and 60 mg/kg, showed a significant decrease of bleeding and ulcer index and alleviated the histopathological changes induced by ethanol such as hemorrhage and necrosis. Ethanol treatment decreased the gastric adhesion mucus content, but a higher level of gastric mucus persisted after preadministration of MCPL. As for the histochemical properties of mucins, marked changes were observed in both the surface and gland mucous cells in ethanol-treated rats, but these changes were detected only in the surface mucous cells in rat preadministered with MCPL. Using conventional methods for mucins, ethanol-treated rats revealed a decrease of neutral and acid mucin in the surface epithelium and mucous neck cells compared with normal rats. A marked decrease of BSL-1 by lectin histochemistry was also revealed in the ethanol-treated rats. But the MCPL preadministered rats showed similar stainabilities and lectin affinity patterns for mucins as the normal rats. These results indicate that pretreatment with MCPL provided protection of the gastric mucosa from ethanol-induced injury by maintaining the mucus barrier in rats.

The anti-inflammatory effects of 2 Hz electroacupuncture with different intensities on acute carrageenan-induced inflammation in the rat paw.

The aim of this study was to investigate the anti-inflammatory effects of low frequency electroacupuncture (EA) with different intensities in carrageenan-injected rat paw. Bilateral 2 Hz EA stimulation with 0.5, 1 and 3 mA were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via needles for 30 min. We first examined the degrees of edema and hyperalgesia using measurements of paw swelling and hot plate latency over 180 min, at 30 min intervals, after the carrageenan injection. The edema and thermal sensitivities of the hind paw induced by a carrageenan-injection were strongly inhibited by EA stimulation, especially at low intensity. At 3 h after carrageenan-injection, we investigated whether the effects of a 2 Hz EA on a carrageenan-induced edema and hyperalgesia are associated with peripheral cyclooxygenase (COX) mRNA induction and prostaglandin E2 (PGE2) synthesis. Although the induction of COX-2 mRNA was inhibited by 2 Hz EA at various intensities, there was no significant change. However, the synthesis of PGE2 induced by a carrageenan injection was significantly attenuated in rat paw with low intensity EA treatment. The data indicate that low frequency EA treatment with relatively low intensity might be a useful therapy for mitigation of inflammatory edema and hyperalgesia through the regulation of COX-2 expression and PGE2 production in a model of peripheral inflammation in rats.

Involvement of ionotropic glutamate receptors in low frequency electroacupuncture analgesia in rats.

The present study was conducted to determine whether blockage of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid/kainate (AMPA/KA) receptors influences the induction of low frequency electroacupuncture (EA) analgesia. Although neither intrathecal injection of NMDA antagonist D-2-amino-5-phosphonopentanoic acid (D-AP-5) or AMPA/KA antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonami-de (NBQX) disodium alone had an effect on analgesia, spinal application of D-AP-5 and NBQX disodium significantly prevented analgesia induced by 2 Hz EA. The intrathecal injection of the excitatory amino acid NMDA produced analgesia for several minutes after intrathecal injection, as did EA stimulation. These results suggest that ionotropic glutamate receptors may be involved in the induction of 2 Hz EA analgesia.

An aqueous extract of Platycodi radix inhibits LPS-induced NF-kappaB nuclear translocation in human cultured airway epithelial cells.

We investigated the effects of aqueous extract from Platycodi radix (AEPR), a traditional drug used to treat acute lung inflammatory disease, on lipopolysaccharide (LPS)-induced inflammation in A549 human cultured airway epithelial cells. Nuclear factor-kappaB (NF-kappaB) and its inhibitory regulator, inhibitory kappaB (I-kappaB), play crucial roles in LPS-induced inflammatory response. We show that LPS-induced nuclear translocation of NF-kappaBp65 is inhibited by AEPR. LPS-induced expression of I-kappaBalpha, which is expressed by LPS-induced activation of NF-kappaB, is inhibited by AEPR as well. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), are repressed by AEPR. We also found that expression of heat shock protein 70 (Hsp70), which has an anti-inflammatory activity, is increased by AEPR plus LPS. These results suggest that AEPR may act as a therapeutic agent for inflammatory disease through regulating the activity of NF-kappaB and expression of inflammatory genes.

The aqueous extract from Artemisia capillaris Thunb. inhibits lipopolysaccharide-induced inflammatory response through preventing NF-kappaB activation in human hepatoma cell line and rat liver.

Artemisia capillaris Thunb. has been used for the remedy of liver diseases such as hepatitis, jaundice and fatty liver in traditional oriental medicine. However, despite extensive pharmacological studies, the molecular mechanism of the anti-inflammatory effect of Artemisia capillaris Thunb. has hardly been studied. In the present study, we investigated the pharmacological action mechanism on LPS-induced liver inflammation in HepG2 human hepatocarcinoma cells and rat liver. Aqueous extract from Artemisia capillaris Thunb. (AEAC) inhibits expression of inflammatory proteins including iNOS, COX-2 and TNF-alpha. Also, nuclear translocation of NF-kappaB and degradation of I-kappaBalpha are blocked by AEAC pretreatment. These results suggest that the inhibitory effect of AEAC on the expression of inflammatory proteins involves suppression of NF-kappaB activation.

Anti-inflammatory effects of aqueous extract from Dichroa febrifuga root in rat liver.

AIM: To study the anti-inflammatory effects of aqueous extract from Dichroa febrifuga root (AEDF) for suppression in the process of lipopolysaccharide (LPS)-induced sepsis in the rat liver. METHODS: The inhibitory effect of AEDF on the alteration of inflammatory proteins was investigated by Western blot and immunohistochemical analysis. RESULTS: Western blot analysis showed that the level of nuclear factor (NF)-kappaBp65 was markedly up-regulated and (I)-kappaBalpha was down-regulated by LPS (8 mg/kg) challenge. However, AEDF 100 mg/kg inhibited induction of NF-kappaBp65 and degradation of I-kappaBalpha in the liver of LPS-challenged rats. Immunohistochemical analysis showed that while the expression of the NF-kappaBp65, tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS) tended to increase, that of I-kappaBalpha was decreased in the hepatocytes of rats challenged with LPS. A slight decline of NF-kappaBp65, TNF-alpha and iNOS, but an increase of I-kappaBalpha were observed in the hepatocytes of the rats pretreated with AEDF. CONCLUSION: AEDF may act as a therapeutic agent for inflammatory disease through a regulation of inflammation-related proteins.

Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells.

Tetrandrine, isolated from the root of Stephania tetrandra, has been used in Chinese medicine for the treatment of silicosis and arthritis, and it also has anti-tumor/growth activities. However, the signaling pathways of tetrandrine-induced growth arrest and apoptosis in cancer cells remain unclear. We investigated the molecular mechanisms of tetrandrine-induced apoptosis and growth arrest in human lung carcinoma cells. Upon treatment with tetrandrine, a time-dependent inhibition of cell growth was observed and cells developed many of the hallmark features of apoptosis. Flow cytometry analysis confirmed that tetrandrine increased populations of both apoptotic sub-G1 and G1 phase. Tetrandrine-induced growth inhibition was associated with induction of Cdk inhibitor p21, inhibition of cyclin D1 and activation of caspase-3. Tetrandrine also affected the expression patterns of cytoskeletons including distribution of F-actin and expression level of microtubule. These results suggest that tetrandrine merits further investigation as a cell cycle blocker as well as a cancer chemopreventive agent.