Pharmacological Activities and Applications of Spicatoside A

Ramalingam, Mahesh,Kim, Sung-Jin The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

Liriopogons (Liriope and Opiopogon) species are used as a main medicinal ingredient in several Asian countries. The Liriopes Radix (tuber, root of Liriope platyphylla) has to be a promising candidate due to their source of phytochemicals. Steroidal saponins and their glycosides, phenolic compounds, secondary metabolites are considered of active constituents in Liriopes Radix. Spicatoside A, a steroidal saponin, could be more efficacious drug candidate in future. In this review, we summarized the available knowledge on phytochemical and pharmacological activities for spicatoside A. It significantly suppressed the level of NF-${\kappa}B$, NO, iNOS, Cox-2, IL-$1{\beta}$, IL-6 and MAPKs in LPS-stimulated inflammation. The production of MUC5AC mucin was increased. MMP-13 expression was down-regulated in IL-$1{\beta}$-treated cells and reduced glycosaminoglycan release from IL-$1{\alpha}$-treated cells. The neurite outgrowth activity, PI3K, Akt, ERK1/2, TrkA and CREB phosphorylation and neurotropic factors such as NGF and BDNF were upregulated with increased latency time. It also showed cell growth inhibitory activity on various carcinoma cells. From this, spicatoside A exerts anti-inflammation, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anticancer activities. Further studies are needed on spicatoside A in order to understand mechanisms of action to treat various human diseases.

The Protective Effects of Insulin on Hydrogen Peroxide-Induced Oxidative Stress in C6 Glial Cells

( Ramalingam Mahesh ),( Sung Jin Kim ) 한국응용약물학회 2009 Biomolecules & Therapeutics(구 응용약물학회지) Vol.17 No.4

Pharmacological Activities and Applications of Spicatoside A

( Mahesh Ramalingam ),( Sung-jin Kim ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

Liriopogons (Liriope and Opiopogon) species are used as a main medicinal ingredient in several Asian countries. The Liriopes Radix (tuber, root of Liriope platyphylla) has to be a promising candidate due to their source of phytochemicals. Steroidal saponins and their glycosides, phenolic compounds, secondary metabolites are considered of active constituents in Liriopes Radix. Spicatoside A, a steroidal saponin, could be more efficacious drug candidate in future. In this review, we summarized the available knowledge on phytochemical and pharmacological activities for spicatoside A. It significantly suppressed the level of NF-kB, NO, iNOS, Cox-2, IL-1b, IL-6 and MAPKs in LPS-stimulated inflammation. The production of MUC5AC mucin was increased. MMP- 13 expression was down-regulated in IL-1b-treated cells and reduced glycosaminoglycan release from IL-1a-treated cells. The neurite outgrowth activity, PI3K, Akt, ERK1/2, TrkA and CREB phosphorylation and neurotropic factors such as NGF and BDNF were upregulated with increased latency time. It also showed cell growth inhibitory activity on various carcinoma cells. From this, spicatoside A exerts anti-inflammation, anti-asthma, anti-osteoclastogenesis, neurite outgrowth, memory consolidation and anticancer activities. Further studies are needed on spicatoside A in order to understand mechanisms of action to treat various human diseases.

Insulin as a Potent Stimulator of Akt, ERK and Inhibin-βE Signaling in Osteoblast-Like UMR-106 Cells

Ramalingam, Mahesh,Kwon, Yong-Dae,Kim, Sung-Jin The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.6

Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-${\beta}E$ in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-${\beta}E$ subunit of the TGF-${\beta}$ family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.

Insulin as a Potent Stimulator of Akt, ERK and Inhibin-bE Signaling in Osteoblast-Like UMR-106 Cells

( Mahesh Ramalingam ),( Yong-dae Kwon ),( Sung-jin Kim ) 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.6

Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-bE in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-bE subunit of the TGF-b family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.

Protective effects of activated signaling pathways by insulin on C6 glial cell model of MPP⁺-induced Parkinson’s disease

Ramalingam, Mahesh,Kim, Sung-Jin Informa UK (Informa Healthcare) 2017 Journal of receptors and signal transduction Vol.37 No.1

<P>Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD) associated with mitochondrial dysfunction mediated by oxidative stress. Astrocytes regulate neuronal function via the modulation of synaptic transmission and plasticity, secretion of growth factors, uptake of neurotransmitters, and regulation of extracellular ion concentrations and metabolic support of neurons. Therefore, this study was undertaken to investigate the mechanism of action of insulin on a 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity of events associated in cell viability and toxicity to the expression profile of cell signaling pathway proteins and genes in rat C6 glial cells. The various concentrations of MPP+ alone inhibited cell viability in a dose-dependent manner. Pretreatment of insulin prevented the cell death and lowered the intracellular reactive oxygen species and calcium ion influx by MPP+. Insulin also suppressed the -synuclein and elevated the insulin signaling pathway molecules IR, IGF-1R, IRS-1 and IRS-2 in C6 cells through phosphorylation of Akt/ERK survival pathways. Moreover, insulin inhibits MPP+-induced Bax to Bcl-2 ratio. These results suggest that insulin has a protective effect on the MPP+-toxicity in C6 glial cells.</P>

Insulin suppresses MPP+-induced neurotoxicity by targeting integrins and syndecans in C6 astrocytes

Ramalingam, Mahesh,Cheng, Mi Hyun,Kim, Sung-Jin Informa UK (TaylorFrancis) 2017 Journal of receptors and signal transduction Vol.37 No.6

Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models

Ramalingam, Mahesh,Kim, Hyojung,Lee, Yunjong,Lee, Yun-Il Frontiers Media S.A. 2018 FRONTIERS IN AGING NEUROSCIENCE Vol.10 No.-

<P>The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of <I>Glycyrrhiza uralensis</I> or <I>G. glabra</I> or <I>G. inflata</I> from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan.</P>

Free radical scavenging activities of <b>Cnidium officinale</b> Makino and <b>Ligusticum chuanxiong</b> Hort. methanolic extracts

Ramalingam, Mahesh,Yong-Ki, Park Medknow Publications 2010 Pharmacognosy magazine Vol.6 No.24

<P><B>Background:</B></P><P>Antioxidants from natural resources possess multifaceted and importance of the activities provides substantial scope in neurodegenerative diseases. The aim of this study was to assess and compare the free radical scavenging activities of <B>Cnidium officinale</B> and <B>Ligusticum chuanxiong</B>, which are closely related species.</P><P><B>Materials and Methods:</B></P><P>The scavenging activities of plant materials were evaluated using Trolox equivalent antioxidant capacity (TEAC), oxygen radical absorbance capacity (ORAC) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide radical (O<SUB>2</SUB>·<SUP>-</SUP>), hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>), hydroxyl (OH·), nitric oxide radical (NO·) and metal chelation. In addition, the cell viability and nitric oxide release were assayed using Neuro-2a (N2a) cells.</P><P><B>Results:</B></P><P>The methanolic extracts of <B>C. officinale</B> and <B>L. chuanxiong</B> showed scavenging activities of free radicals with an additional antioxidant capacity. Moreover, the efficacy on the cell viability and nitric oxide release in cell culture model has been established.</P><P><B>Conclusion:</B></P><P>Results of the present study suggests that the extracts of <B>C. officinale</B> and <B>L. chuanxiong</B> have comparatively similar free radical scavenging activities <I>in vitro</I> and may have important health effects.</P>

Effect of Aerva lanata against oxalate mediated free radical toxicity in urolithiasis

Begum, Vava Mohaideen Hazeena,Mahesh, Ramalingam,Ramesh, Thiyagarajan,Soundararajan, Periasamy Kyung Hee Oriental Medicine Research Center 2008 Oriental pharmacy and experimental medicine Vol.8 No.1

This study was undertaken to evaluate the antioxidant potential of A. lanata on oxalate mediated free radical toxicity in ethylene glycol induced calcium oxalate urolithic rats. Calcium oxalate (CaOX) stone was induced by 0.75% ethylene glycol in drinking water for 28 days. From $29^{th}$ day onwards, the CaOX urolithic rats were treated with A. lanata aqueous suspension (2,000 mg/kg body weight/dose/day) orally for another 28 days. At the end of experimental periods the animals were sacrificed, samples were collected and analyzed the lipid peroxidation product, protein oxidation product, enzymatic and non-enzymatic antioxidants in normal and experimental groups. Lipid peroxidation and protein oxidation products were significantly elevated while enzymatic and non-enzymatic antioxidant levels were significantly decreased in ethylene glycol induced CaOX urolithic rats when compared with control rats. The above alterations were reverted to near control in rats treated with aqueous suspension of A. lanata. This study suggests that A. lanata could prevent the free radical formation from calcium oxalate urolithiasis in rats and protecting the renal cells from oxidative injury.