Embryos Of Lotus Research Articles

In vitro acute gamma radiation on tissue of pink and white lotus (Nelumbo nucifera Gaertn.) in Thailand

This research aimed to investigatethe age of embryos of pink and white lotus for in vitropropagation and examine the sensitivity of young lotus plants derived from tissue culture to acute gamma radiation. The seeds of both lotus varieties were 4-week, 6-week and 8-week-old embryos cultivated on solid MS medium. They were then transferred to solid MS medium supplemented with 3 mg/L BA. After culturing, the 6-week-old pink lotus embryos had an average maximum petiole length of 16.78 ± 1.01 cm and an average of 11.84 ± 0.44 roots/explant, while the 6-week-old white lotus embryos had an average maximum petiole length of 15.48 ± 0.68 cm and an average of 11.76 ± 0.70 roots/explant. Each young lotus plant produced one shoot. After treating the young lotus plants with liquid MS medium supplemented with 3 mg/L BA, both lotus varieties showed increased shoot numbers at 3.54 ± 0.13 and 3.40 ± 0.91 shoots/explant. Young lotus plants of both varieties were exposed to gamma radiation levels of 0, 20, 30 and 40 Gy. The LD50 value for pink lotus was 26.138 Gy, while the LD50 value for the white lotus was 32.031 Gy.The LD50 value will offer vital information for determining the optimal dosage of gamma radiation for both pink and white lotus in vitro.

Neferine, a novel ROCK1-targeting inhibitor, blocks EMT process and induces apoptosis in non-small cell lung cancer.

The compounds derived from Traditional Chinese Medicines have shown various pharmacological activities with unique advantages, especially in the aspect of antitumor. Neferine (Nef), a natural compound, extracted from green seed embryos of Lotus (Nelumbo nucifera Gaertn.) also exerts antitumor effects on cancers. In this study, the effects and mechanisms of Nef on epithelial-to-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC) were evaluated. The results showed that Nef had the antitumor effects in vivo and in vitro. Nef significantly suppressed cell viability and induced apoptosis in NSCLC cells, with elevated reactive oxygen species and reduced BCL2/BAX ratio. Nef was also demonstrated to inhibit the invasion, metastasis and EMT process of NSCLC cells, and attenuate EMT-related changes of E-cadherin, N-cadherin and Vimentin at both transcriptional and translational levels. Moreover, we concluded that the inhibitory effects of Nef on EMT was achieved by targeting Rho-associated protein kinase 1, a protein mediating the process of EMT in various cancers. These results showed that Nef had a significant antitumor effect on NSCLC cells by inducing apoptosis and blocking EMT, providing the therapeutical prospect on NSCLC treatment.

Inhibitory Effect of Lotusine on Solar UV-Induced Matrix Metalloproteinase-1 Expression

Solar ultraviolet (sUV) radiation remains a major cause of skin aging. Nelumbo nucifera (lotus) is a well-known edible plant widely grown in Asia, including Korea, China, and Japan. The lotus consists of flowers, leaves, stems, and seeds, and all parts reportedly possess nutritional and medical values. Traditionally, lotus flowers, leaves, stems, and seeds have been used as antidiarrheal agents, diuretics, antipyretics, and antimicrobial and antihyperlipidemic agents. In addition, the Nelumbo nucifera lotus embryo has been shown to possess sedative and antipyretic properties and can relieve hemostatic thirst and treat eye diseases. Recently, Nelumbo nucifera lotus flower extract has been widely used in cosmetics due to its ability to reduce wrinkles and its whitening effects. Numerous cosmetics using Nelumbo nucifera lotus embryo extracts are commercially available. However, the active components of Nelumbo nucifera remain elusive. Lotusine is a phytochemical and soluble alkaloid found in lotus embryos. Herein, we examined the anti-wrinkle effect of lotusine using sUV-exposed human keratinocytes. We observed that lotusine reduced sUV-induced matrix metalloproteinase (MMP)-1 expression and modulated transcriptional activities of activator protein (AP)-1 and nuclear factor kappa B (NF-κB). sUV-induced AP-1 and NF-κB activity could be activated via multiple signal transduction cascades, including the p38 MAPK, JNK, ERK1/2, and Akt pathways in the skin. Lotusine inhibited the MEK1/2-ERK1/2-p90RSK, MKK3/6-p38, and Akt-p70S6K pathways. Overall, our findings suggest that lotusine has potential benefits related to MMP-1 expression and skin aging following sUV exposure. Hence, the lotus can be developed as a valuable functional food and cosmetic material.

A review on Extraction of alkaloid from Nelumbo nucifera Embryos and Leaves for Production of Dietary Supplement

Lotus (Nelumbo nucifera Gaertn.) commonly distributed in low-lying and flooded areas like Southern Vietnam provides flowers, leaves, seeds, embryos, and edible rhizomes. All parts of the plant show good pharmacokinetic properties, especially lotus embryos and leaves. Studies have shown that lotus plums and leaves have many bioactive compounds such as alkaloids, flavonoids, triterpenoids, and polyphenols, in which alkaloids are one of mainly bioactive compound kinds. So that, there are many studies investigating extraction methods that increase the amount of alkaloid from lotus leaves, embryos. There are some conventional extract methods such as soak, heat reflux, Soxhlet, etc… and some modern extract methods as microwave, ultrasounds, enzyme assisted, supercritical fluids (S-CO2). At present, lotus leaves, embryos and their bioactivities can have application potential in the supplementary food such as protect-liver, anti-neurotic, etc.. The aim of this paper is to review a variety of develop methods used in the alkaloid extraction from lotus embryos, leaves. Besides, this study also introduces some pharmacokinetic properties of alkaloid which can use in functional foods.

Neferine Protects Against Brain Damage in Permanent Cerebral Ischemic Rat Associated with Autophagy Suppression and AMPK/mTOR Regulation.

Neferine is the major alkaloid compound isolated from the seed embryos of lotus. Neferine has many pharmacological effects, such as anti-inflammatory, antioxidative stress, and antiapoptotic effects, and it maintains autophagic balance. The purpose of this study was to explore the mechanism by which neferine attenuates autophagy after permanent cerebral ischemia in rats. We performed permanent cerebral ischemia in rats by middle cerebral artery occlusion (pMCAO) for 12h with or without administration of neferine or nimodipine, a calcium (Ca2+) channel blocker. Neuroprotective effects were determined by evaluating the infarct volume and neurological deficits. Autophagy and its signaling pathway were determined by evaluating the expression of phosphorylated AMP-activated protein kinase alpha (AMPKα), phosphorylated mammalian target of rapamycin (mTOR), beclin-1, microtubule-associated protein 1A/1B-light chain 3 class II (LC3-II), and p62 by western blotting. Autophagosomes were evaluated by transmission electron microscopy. Neferine treatment significantly reduced infarct volumes and improved neurological deficits. Neferine significantly attenuated the upregulation of autophagy-associated proteins such as LC3-II, beclin-1, and p62 as well as autophagosome formation, all of which were induced by pMCAO. Neferine exerted remarkable protection against cerebral ischemia, possibly via the regulation of autophagy mediated by the Ca2+-dependent AMPK/mTOR pathway.

Chemomodulatory effect of neferine on DMBA-induced squamous cell carcinogenesis: Biochemical and molecular approach.

Neferine (NEF) is nontoxic, bisbenzylisoquinoline alkaloid is derived from the seed embryo of lotus, a familiar medicinal plant. Although several mechanisms have been planned, an evident antitumor action pathway of NEF on the oral tumor is still not known. In the current study, we aimed at investigating the protecting effect of NEF against experimental oral carcinoma and clarify its possible mechanism through the induction of apoptosis, proliferation, and inflammatory signaling pathways. The experimental hamsters were divided into four groups (I-IV) containing six hamsters each. The group I was control group, group II and III hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA) (0.5%) alone, thrice in a week for 10 weeks, and group III and IV hamsters received oral supplementation of NEF at a concentration of 15 mg/kg bw. All the hamsters were sacrificed after 16 weeks. Our results revealed that DMBA treated hamsters exhibited 100% oral tumor cell formation with high-tumor incidence (TI), tumor number (TN), tumor volume (TV), decreased levels of antioxidants, increased status of lipid peroxidation (LPO), and modulated the activities of liver marker agents as well as NF-kB, cell proliferation (PCNA), and p53 proteins. NEF supplementation in DMBA treated hamsters, resulted in delayed lesion synthesis, and brought back the levels of the biochemical parameters. In addition, immunostaining of NF-kB, PCNA, and p53 showed that they were inhibited by NEF. Thus, NEF might be considered a better chemopreventive drug in an experimental model of home-based primary care (HBPC). More research is necessary to study other pathways implicated in oral carcinomas and their modulation by NEF.

Neferine alleviates P2X3 receptor in rat dorsal root ganglia mediated neuropathic pain

Chronic neuropathic pain is caused by tissue damage or nervous system inflammation and is characterized by sensitivity to painful stimuli. P2X3 receptors play an important role in facilitating pain transmission. Neferine is a bisbenzylisoquinline alkaloid isolated from seed embryos of lotus, which has anti-inflammatory and anti-oxidation pharmacological functions. The present research investigated whether neferine relieves neuropathic pain related to the P2X3 receptor in rat dorsal root ganglia (DRGs). Chronic contraction injury (CCI) in rats was used as a model for neuropathic pain. The results indicated that the expression of P2X3 receptor was significantly increased in the DRGs of CCI rats and that mechanical allodynia and thermal hyperalgesia were also enhanced in CCI rats. Neferine markedly lowered the upregulated P2X3 receptor and interleukin-1beta, inhibited the phosphorylation and activation of ERK1/2 in the DRGs of CCI rats, and relieved neuropathic pain. Therefore, neferine alleviates neuropathic pain by downregulating the expression of P2X3 receptor.

Elucidation the binding mechanism of Nelumbo nucifera-derived isoquinoline alkaloids as Rho-kinase 1 inhibitors by molecular docking and dynamic simulation

Rho-kinase 1 (ROCK1) is a key molecular target for controlling smooth muscle (SM) contraction in asthma, gastrointestinal disorders, hypertension. Embryos of lotus seed (Nelumbo nucifera) are traditional folk herbs widely used in treating various diseases which are closely related to SM contraction. With the aim of explaining the mechanism of embryos of lotus seed, 27 isoquinoline alkaloids were isolated from the embryos of lotus seed, the inhibitory activity of these alkaloids against ROCK1 were virtual screened via molecular docking and molecular dynamics (MD) simulations. The docking results indicated that 5 bisbenzylisoquinolines (BBIs) and 1 tribenzylisoquinoline (TBI) were potent inhibitors with high binding affinity for both A and B chains of ROCK1 (AcRock and BcRock). The MD results also revealed that neoliensinine (28) was the most potent inhibitor, which was corresponding to the irreversible relaxation effect of neoliensinine on SM. Moreover, through the MD simulation, it also indicated that neoliensinine (28) interacted in its stretched conformation through polar solvation interactions and van der Waal forces. Finally, with the best calculation results, the inhibition effect of neoliensinine (28) on the contraction of vascular smooth muscle cells (VSMCs) and ROCK1 was also confirmed by several biological tests.Communicated by Ramaswamy H. Sarma

Neferine in the LotusPlumule Potentiates the Antitumor Effect of Imatinib in Primary Chronic Myeloid Leukemia Cells In Vitro.

Imatinib, the prototype BCR-ABL tyrosine kinase inhibitor (TKI), is the first-line treatment for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase. However, a subgroup of patients exhibit poor response or experience relapse. This issue may be overcome by combination therapy using natural compounds. Neferine, a major bisbenzylisoquinoline alkaloid extracted from "lotus plumule" (seed embryo of lotus) commonly used in traditional Chinese medicine and tea, was used herein in the combination treatment of CML. The MTT assay showed that neferine exerted cytotoxicity in primary CML cells in a dose-dependent manner. Moreover, low concentrations of neferine (4 and 8 µM) sensitized primary CML cells to imatinib (CI < 1), and significantly decreased its IC50 from 0.70 ± 0.10 to 0.32 ± 0.06 µM and 0.16 ± 0.02 µM, respectively. Cotreatment of neferine and imatinib significantly decreased the expression of BCR-ABL protein and its molecular chaperone heat shock protein 90 (Hsp90) mRNA and protein levels, and further decreased phospho-extracellular regulated protein kinase 1/2 (p-Erk1/2) and myeloid cell leukemia (Mcl-1) expression. These results suggest that neferine might be a potential imatinib sensitizer in CML treatment. PRACTICAL APPLICATION: In China, Lotus plumule, the green embryo of lotus, is used as a tea and as a source of herbal medicine in the treatment of anxiety, insomnia, spermatorrhea, and thirst. Additional, neferine, a bisbenzylisoquinoline alkaloid extracted from lotus plumule has been shown to have antitumor potential. Herein, the effect of neferine and imatinib cotreatment on primary CML cells obtained from CML patients was assessed, with a synergisticeffect being observed between the two compounds. Therefore, neferine might be a promising natural compound to potentiate imatinib in CML patients.

Antioxidative and antiphotoaging activities of neferine upon UV-A irradiation in human dermal fibroblasts.

Our daily exposure to ultraviolet radiation (UVR) results in the production of reactive oxygen species (ROS), lipids, proteins and DNA damage and alteration in fibroblast structure, thus contributing to skin photoaging. For this reason, the use of natural bioactive compounds with antioxidant activity could be a strategic tool to overcome ultraviolet A (UV-A) induced deleterious effect. Neferine is an alkaloid extract from the seed embryos of lotus (Nelumbo nucifera Gaertn). In the present study, we report the protective effect of neferine against UV-A induced oxidative stress and photoaging in human dermal fibroblasts (HDFs). HDFs subjected to UV-A irradiation showed increased production of ROS and malondialdehyde (MDA). Furthermore, it depleted the cellular enzymatic antioxidant superoxide dismutase (SOD) and non-enzymatic antioxidant glutathione peroxidase (GPx). On the other hand, HDFs treated with neferine followed by UV-A irradiation reversed the process, reduced the ROS and lipid peroxidation and restored the antioxidants pool. Moreover, neferine treatment significantly inhibited UV-A induced matrix metalloproteinase-1 (MMP-1) expression in HDFs. Remarkable morphological and ultrastructural alterations observed in HDFs upon UV-A irradiation, were also reduced with neferine treatment. Taken together, our results suggest that neferine has strong antioxidative and photoprotective properties and thus may be a potential agent for the prevention and treatment of UV-A mediated skin photoaging.

FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells.

Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability. In an effort to determine the molecular mechanisms in neferine-incubated IMR32 cells, cell cycle arrest, cell migration, and focal adhesion kinase (FAK), the 70-kDa ribosomal S6 kinase 1 (S6K1), poly (ADP-ribose) polymerase (PARP), caspase-3, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein expressions were investigated. Neferine strongly disrupted the neuroblastoma cell growth via induction of G2/M phase arrest. Furthermore, neferine provoked autophagy and apoptosis in IMR32 cells, confirmed by p-FAK, and p-S6K1 reduction, LC3-II accumulation, Beclin-1 overexpression, and cleaved caspase-3/PARP improvement. Finally, neferine markedly retarded cell migration of neuroblastoma cancer cells. As a result, our findings for the first time showed an explicit anti-cancer effect of neferine in IMR32 cells, suggesting that neferine might be a potential candidate against human neuroblastoma cells to improve clinical outcomes with further in vivo investigation.

Neferine suppresses diethylnitrosamine-induced lung carcinogenesis in Wistar rats

Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus which has attracted attention for its anti-inflammatory and anti-cancer activities. The aim of this study was to evaluate the anti-cancer effect of neferine against diethylnitrosamine (DEN)-induced lung carcinogenesis in Wistar rats and to explore the underlying molecular mechanism. DEN-induced oxidative stress is mediated by alterations in the levels of pulmonary reactive-oxygen species, lipid peroxidation, protein carbonyl content and antioxidant status. Thus, treatment with neferine restored cellular normalcy, highlighting the antioxidant potential of neferine in mitigating the oxidative stress-mediated damage produced during DEN-induced lung carcinogenesis. Histopathological analysis showed disorganized alveolar structure, thickened alveolar wall, infiltration of inflammatory cells in DEN-induced rats, the damage was significantly reduced upon neferine treatment. DEN-induced rats exhibited increased gene expression of NF-κB, COX-2, CYP2E1, VEGF, Bcl-2, PI3K/AKT/mTOR and significantly decreased the gene expression of p53, Bax, caspase-9 and caspase-3. Neferine treatment restored the DEN- induced alteration of these gene expression levels. Further, blotting analysis also revealed increased expression of NF-κB, COX-2, Bcl-2 and decreased expression of Bax, caspase-9 and caspase-3 proteins in DEN-induced rats. Neferine treatment restored the expression of these proteins in DEN- induced lung carcinogenesis.

Isolation and identification of a tribenzylisoquinoline alkaloid from Nelumbo nucifera Gaertn, a novel potential smooth muscle relaxant

A new skeleton benzylisoquinoline (BI) named neoliensinine (1) was isolated from embryos of lotus seed (Nelumbo nucifera Gaertn.), a traditional Chinese herb. The tribenzylisoquinoline (TBI) structure of 1 was confirmed by interpreting spectroscopic data of UV, IR, MS, 1D and 2D NMR. The stereo-configurations of the new compound, together with two known bisbenzylisoquinolines (BBI), neferine and isoliensinine were established by analyzing 1H NMR and 13C NMR spectra. The relaxation of 1, neferine, isoliensinine and liensinine in isolated mesenteric vascular smooth muscle (VSM) was evaluated. All the four BIs could efficiently inhibit MVSM contraction induced by 124mM KCl, with IC50 values of 2.407μM (1), 1.169μM (neferine), 3.504μM (isoliensinine) and 3.583μM (liensinine), respectively, suggesting that they were all potential relaxants for abnormal smooth muscle contractions. Interestingly, VSM treated by the three BBIs could re-contract when being stimulated by KCl after the drugs were removed, while VSM dealt with the TBI couldn't. It indicated that 1 has much high affinity with the molecular targets on relaxation of VSM contraction, which may relate to the unique skeleton with three BI groups.

Flavonoids of Lotus (Nelumbo nucifera) Seed Embryos and Their Antioxidant Potential.

Flavonoids from lotus (Nelumbo nucifera) seed embryos were fractionated over a macroporous resin chromatography into 2 main fractions (I and II), and subsequently identified by high-performance liquid chromatography coupled with tandemmass spectrometry (HPLC-MS2 ). Sixteen flavonoids were identified in lotus seed embryos, including 8 flavonoid C-glycosides and 8 flavonoid O-glycosides, in which the flavonoid C-glycosides were the main flavonoids. Among them, 2 flavonoid O-glycosides (luteolin 7-O-neohesperidoside and kaempferol 7-O-glucoside) were identified in lotus seed embryos for the 1st time. For further elucidating the effects of flavonoid C-glycosides to the bioactivities of lotus seed embryos, we compared the differences of the flavonoids and their antioxidant activities between leaves and seed embryos of lotus using the same methods. The results showed the antioxidant activity of flavonoids in lotus seed embryos was comparable or higher than that in lotus leaves, whereas the total flavonoid content in seed embryos was lower than lotus leaves which only contained flavonoid O-glycosides. The flavonoid C-glycosides of lotus seed embryos had higher antioxidant properties than the flavonoid O-glycosides presented in lotus leaves. This study suggested that the lotus seed embryos could be promising sources with antioxidant activity and used as dietary supplements for health promotion.

Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells.

Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond donor, acceptor, hERG IC50, logp, logD were considered for the QSAR analyses. Neferine revealed higher toxicity toward paclitaxel- and doxorubicin-resistant breast, lung or colon cancer cells, implying collateral sensitivity of these cells toward neferine. Increased R123 uptake was observed in a comparable manner to the control P-gp inhibitor, verapamil. Molecular docking analyses revealed that neferine still interacts with P-gp, even if R123 was pre-bound. Bioinformatical ADME and toxicity analyses revealed that neferine possesses the druggability parameters with no predicted toxicity. In conclusion, neferine may allocate the P-gp drug-binding pocket and prevent R123 binding in agreement with P-gp inhibition experiments, where neferine increased R123 uptake.

Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice.

Cardiac fibrosis is a common pathological process accompanying diabetes mellitus. In this report, we studied the effects of neferine (a major bisbenzylisoquinline alkaloid derived from lotus embryos) on cardiac fibrosis induced by diabetes mellitus, as well as the underlying molecular pathways. In vivo, type 1 diabetes mellitus was induced in mice by administering streptozotocin. Diabetic mice were treated with neferine through oral gavage, and cardiac function was assessed using echocardiography. Total collagen deposition was assessed by Masson's trichrome and Picrosirius staining. In vitro, cardiac fibroblasts were cultured in normal or high-glucose medium with or without neferine. Neferine attenuated left ventricular dysfunction and remodeling and reduced collagen deposition in diabetic mice. In vitro, neferine inhibited cardiac fibroblast proliferation, migration, and differentiation into myofibroblasts. In addition, neferine reduced high-glucose-induced collagen production and inhibited TGF-β1-Smad, ERK and p38 MAPK signaling activation in cardiac fibroblasts. These results suggest that neferine may have antifibrogenic effects in diabetes-related cardiac fibrosis.

Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation.

Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.

Isoliensinine induces apoptosis in triple-negative human breast cancer cells through ROS generation and p38 MAPK/JNK activation.

Isoliensinine, liensinine and neferine are major bisbenzylisoquinoline alkaloids in the seed embryo of lotus (Nelumbo nucifera), and exhibit potential anti-cancer activity. Here, we explored the effects of these alkaloids on triple-negative breast cancer cells and found that among the three alkaloids isoliensinine possesses the most potent cytotoxic effect, primarily by inducing apoptosis. Interestingly, isoliensinine showed a much lower cytotoxicity against MCF-10A, a normal human breast epithelial cell line. Further studies showed that isoliensinine could significantly increase the production of reactive oxygen species (ROS) in triple-negative breast cancer cells, but not in MCF-10A cells. The isoliensinine-induced apoptosis could be attenuated by radical oxygen scavenger N-acetyl cysteine, suggesting that the cytotoxic effect of isoliensinine on cancer cells is at least partially achieved by inducing oxidative stress. We found that both p38 MAPK and JNK signaling pathways were activated by isoliensinine treatment and contributed to the induction of apoptosis. Furthermore, inhibitors or specific siRNAs of p38 MAPK and JNK could attenuate apoptosis induced by isoliensinine. However, only the p38 inhibitor or p38-specific siRNA blocked the elevation of ROS in isoliensinine-treated cells. Our findings thus revealed a novel antitumor effect of isoliensinine on breast cancer cells and may have therapeutic implications.

Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells

Doxorubicin (DOX) is the best anticancer agent that has ever been used, but acquired tumor resistance and dose limiting toxicity are major road blocks. Concomitant use of natural compounds is a promising strategy to overcome this problem. Neferine, a proven anticancer agent is found in green embryos of lotus seed. The study demonstrates that neferine acts as an effective enhancer of DOX-induced cell death in A549 cells through ROS mediated apoptosis with MAPK activation and inhibition of NF-κB nuclear translocation. Cotreatment of cells with neferine significantly enhanced intracellular DOX-accumulation. Neferine and DOX in combination also triggered oxidative stress through intracellular Ca2+ accumulation and dissipation of mitochondrial membrane potential in addition to significant loss of cellular antioxidant pool. The MAPK inhibitor effectively decreased the cell-death induced by neferine and DOX. Pretreatment of cells with glutathione reversed the apoptosis induced by combined regimen and recovered the Bcl2/Bax ratio. Moreover, neferine treatment significantly increased the cell viability of DOX-treated cardiomyocytes indicating a possible protective role of neferine towards DOX-induced cardiotoxicity. Taken together, our results suggest that a strategy of using neferine and DOX in combination could be helpful to increase the efficacy of DOX and to achieve anticancer synergism by curbing the toxicity.

Experimental study of embryo differentiation in angiosperms

By comparison of peony and lotus embryos in &lt;em&gt;in vitro&lt;/em&gt; culture we established differences in their morphogenetic potential. We traced in peony embryo culture: embryogenesis, embryoidogenesis, organogenesis and histogenesis, whereas the lotus embryo enhibited only one pathway of development - embryogenesis. At the critical stage the embryo becomes independent of the maternal organism, i.e, self-sufficient. Self-sufficiency of the lotus embryo on the 4O-11th day after pollination correlates with development and greening of the first -lead in the plumule, with a sharp increase in embryo dry weight and content of carbohydrates, decrease in the size of the endosperm, degeneration of the inner integument, appearance of starch in the embryo and ovary walls an Increase of its content in the outer integument.