Molecular networking-assisted isolation of chlorophenolic glycosides from the rhizomes of Curculigo orchioides and their inhibitory effect on α-glucosidase.

Molecular networking analysis and in silico tools, such as Network Annotation Propagation (NAP) and MolNetEnhancer, were applied to explore bioactive constituents present in the ethyl acetate-soluble fraction of the rhizomes of Curculigo orchioides. Among the molecular networks, the most abundant cluster was classified as a phenolic glycoside using the ClassyFire module of MolNetEnhancer. Further, the major node in this cluster was accurately predicted as curculigine A using the in silico fragment analysis tool, NAP. Six undescribed chlorophenolic glycosides (1-6) and 11 known phenolic glycosides were isolated, using molecular networking-assisted isolation methods, and their structures were elucidated using 1D, 2D-NMR and HRESIMS. In particular, the structures of the isolated chlorophenolic glycosides, which have non-protonated aromatic rings, were determined using various NMR experiments, such as 1D-selective NOE, ROESY, and LR-HMBC, and acid hydrolysis. All isolated compounds were examined to determine their inhibitory effects on α-glucosidase and compounds 3, 8, 10, 11, 13, 14, and 16 revealed the IC50 values ranging from 19.6 to 35.5 µM. Their structure-activity relationships were also evaluated based on the analysis of their inhibitory effects and performance of molecular docking simulations.

Discrimination of Curculigo orchioides Rhizoma and Curculigo glabrescens Rhizoma using stable isotope and mineral element analyses coupled with chemometrics.

Correct species identification is crucial for ensuring the quality, safety, and efficacy of herbal medicine. Market research indicates that Curculigo glabrescens Rhizoma (CGR) was the major counterfeit of the medicine Curculigo orchioides Rhizoma (COR). To accurately discriminate COR and CGR remains a challenge, and it becomes even more difficult when the herbs have been heavily processed into a powder. In this work, combined with high performance liquid chromatography analysis, a novel component in CGR was discovered, and two stable isotopes (N%, C%, δ15N, δ13C) and nineteen mineral elements were determined along with multivariate statistical analysis to distinguish the authentic COR samples and counterfeit CGR samples. The results showed that there were significant differences between the mean value of N%, δ15N and δ13C according to the botanical origins. In addition, these two species can be differentiated by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) analysis. A linear discriminant analysis (LDA) model with a good classification rate (100%) and cross-validation rate (100%) was established. Hence, stable isotope and mineral element contents combined with chemometrics analysis could be considered as an effective and reliable method for discriminating the source species of COR and CGR.

Structural characterization and anti-osteoporosis activity of two polysaccharides extracted from the rhizome of Curculigo orchioides.

Curculigo orchioides is widely used to treat osteoporosis in China. In this study, we identified the active substances in the crude polysaccharide (CO50) from C. orchioides that had anti-osteoporosis activity in vivo. Two polysaccharides, COP50-1 and COP50-4, were purified from CO50. Based on structural analysis, COP50-1 was composed of α-D-Glcp-(1→, ß-D-Galp-(1→, →4)-α-D-Glcp-(1→, →3,4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →4,6)-ß-D-Manp-(1→, whereas COP50-4 was composed of α-L-Araf-(1→, →2)-α-L-Rhap-(1→, ß-D-Manp-(1→, α-D-Galp-(1→, →2,4)-α-L-Rhap-(1→, →2)-ß-D-Manp-(1→, →4)-α-D-GlcAp-(1→, →3)-α-D-GalAp-(1→, →4,6)-α-D-Galp-(1→, →2,3,6)-ß-D-Manp-(1→, →2,3,5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→ and →3)-α-D-Galp-(1→. Pharmacological assessment revealed that COP50-1 had no obvious osteogenic activity. However, COP50-4 (0.5 µM) significantly enhanced the differentiation and mineralization of osteoblasts in vitro. Moreover, the effect of COP50-4 was greater than that of 17ß-estradiol. Therefore, COP50-4 may be an effective component of CO50 that has great potential for development as an alternative drug for the treatment of osteoporosis.

GC-MS analysis of curculigo orchiodes and medicinal herbs with cytotoxic, hepatoprotective attributes of ethanolic extract from Indian origin.

OBJECTIVES: Liver illnesses are a major public health issue all over the world. Medicinal plants constituents a viable alternative for the development of phytopharmaceuticals with hepatoprotective activity in order to solve some of these health-related problems. The present study is focused on the phytochemical and biological investigation on Indian traditional medicinal plant extracts, for their cytotoxic and hepatoprotective activity. The isolated compounds showed the presence of phenolic constituents which lead to cytotoxicity and hepatoprotective activity of medicinal plant. Cancer causes about 13% of all human deaths in 2007 (7.6 million) (American Cancer Society and WHO December 2006-07). The American Cancer Society estimates that 12,990 new cases of cervical cancer will be diagnosed in the United States year 2016. Cancer-related deaths are expected to increase, with an estimated 11.4 million deaths in 2030. METHODS: The ethanolic extracts of Centella asiatica, Myristica fragrans, Trichosanthes palmata, Woodfordia fruticosa, Curculigo orchioides were evaluated against HEP-G2 cell lines for hepatoprotective activity and Curculigo orchioides was further promoted for the isolation of secondary metabolites based on inhibitory concentration. RESULTS: The ethanolic extracts of C. asiatica, M. fragrans, T. palmata, W. fruticosa, Curculigo orchioides shown significant cytotoxic activity (IC50≤100 µg/mL). The plant extracts also shown significant hepatoprotective activity in a dose dependent manner when tested against HEP-G2 cell lines and cytotoxicity studies against HeLa and HEP-G2 cells. CONCLUSIONS: The extract of Curculigo orchiodes rhizome showed significant cytotoxicity results. Hence the Curculigo orchiodes rhizome was selected for further phytochemical studies to isolate active compounds and their Characterization by GCMS.

Phytochemistry and Pharmacological Activity of Plants of Genus Curculigo: An Updated Review Since 2013.

The genus Curculigo, as a folk herbal medicine, has been used for many years in China, treating impotence, limb limpness, and arthritis of the lumbar and knee joints. The last systematic review of the genus Curculigo was written in 2013, scientifically categorizing the phytochemistry and biological activities. Hitherto, the original compounds and their pharmacological activities were presented as the development of this genus, but there is not an updated review. To conclude the progression of the genus Curculigo, we collected the new literature published from 2013 to 2021 in PubMed, Web of Science, Google Scholar databases, and the Chinese National Knowledge Infrastructure. The novel chlorophenolic glucosides, curculigine, phenolic glycosides, orcinosides and polysaccharides were isolated from Curculigo. The new analyzing methods were established to control the quality of Curculigo as a herbal medicine. In addition, the pharmacological effects of Curculigo focused on anti-diabetes, antibacterial, anti-inflammatory, osteoporosis, antioxidation, etc. The antitumor and neuroprotective activities were newly explored in recent years. The application of herbal medicine was gradually developed in scientific methods. The medicinal value of the genus Curculigo needs to further investigate its pharmacological mechanisms. This new review offers more insights into the exploitation of the pharmacological value of the genus Curculigo.

Inhibitory evaluation of Curculigo latifolia on α-glucosidase, DPP (IV) and in vitro studies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus.

The inhibition of α-glucosidase and DPP enzymes capable of effectively reducing blood glucose level in the management of type 2 diabetes. The purpose of the present study is to evaluate the inhibitory potential of α-glucosidase and DPP (IV) activity including with the 2-NBDG uptake assay and insulin secretion activities through in vitro studies. The selected of active compounds obtained from the screening of compounds by LC-MS were docked with the targeted enzyme that involved in the mechanism of T2DM. From the results, root extracts displayed a better promising outcome in α-glucosidase (IC50 2.72 ± 0.32) as compared with the fruit extracts (IC50 3.87 ± 0.32). Besides, root extracts also displayed a better activity in the inhibition of DPP (IV), enhance insulin secretion and glucose uptake activity. Molecular docking results revealing that phlorizin binds strongly with α-glucosidase, DPP (IV) and Insulin receptor (IR) enzymes with achieving the lowest binding energy value. The present work suggests several of the compounds have the potential that contribute towards inhibiting α-glucosidase and DPP (IV) and thus effective in lowering post-prandial hyperglycaemia.

Prediction of Targets of Curculigoside A in Osteoporosis and Rheumatoid Arthritis Using Network Pharmacology and Experimental Verification.

PURPOSE: Network pharmacology is considered to be the next-generation drug development model that uses bioinformatics to predict and identify multiple drug targets and interactions in diseases. Here, network pharmacology was used to investigate the mechanism by which Curculigoside A (CA) acts in rheumatoid arthritis (RA) and osteoporosis. METHODS: First, TCMSP and SwissADME were applied to predict the druggability of CA. Then, potential targets were identified from overlapping data in SwissTarget and TargetNet, and targets were analyzed using Genemania and DAVID6.8 to obtain information about the GO and KEGG pathways. Ultimately, the drug-target-pathway network was identified after using Cytoscape 3.0 for visualization. Besides, qPCR was used to validate the predicted five major genes targets (EGFR, MAP2K1, MMP2, FGFR1, and MCL1). RESULTS: The results of TCMSP and SwissADME demonstrated that CA exhibits good druggability; 26 potential protein targets were classified by SwissTarget and TargetNet. The results of Genemania and DAVID6.8 indicated that CA probably caused anti-osteoporosis and anti-RA effects by regulating some biological pathways, especially nitrogen metabolism, estrogen signaling pathway, Rap1 signaling pathway, and PI3K/Akt signaling pathway. Besides, the result of Cytoscape 3.0 showed that the 26 targets participate in osteoporosis and RA-related pathways, metabolism, and other physiological processes. In vitro induced inflammation cell model experiments, the qPCR results showed that CA pretreatment significantly decreased the expression of EGFR, MAP2K1, MMP2, FGFR1, and MCL1 genes. CONCLUSION: These results suggested that network pharmacology may provide possible mechanism of how CA exerts therapeutic effects in osteoporosis and RA.

Structural Elucidation and Total Synthesis of Three 9-Norlignans from Curculigo capitulata.

Capitulactones A-C, three unprecedented 9-norlignans featuring a unique 3,5-dihydrofuro[2,3- d]oxepin-7(2 H)-one scaffold, were isolated from the roots of Curculigo capitulata. Their structures with absolute configurations were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. Biomimetic total syntheses of three pairs of the corresponding enantiomers were achieved in 9-10 steps with overall yields of 14.8, 12.7, and 10.3%, respectively. Notably, the unique scaffold of the common western hemisphere of the molecules was constructed by using the oxidation-reduction strategy from benzodihydrofuran.

Structural elucidation and anti-osteoporosis activities of polysaccharides obtained from Curculigo orchioides.

Curculigo orchioides, is a traditional Chinese medicine, is used in strengthening tendons and bones. We evaluated the anti-osteoporosis activity of the crude polysaccharide (CO70) isolated from the rhizomes of C. orchioides in ovariectomized rats. CO70 showed excellent anti-osteoporosis activity comparable to that of 17ß-estradiol. To explore the constituents responsible for the anti-osteoporosis activity of CO70, a novel homogeneous heteropolysaccharide, COP70-3, was isolated and purified from CO70. COP70-3 has a main backbone chain of (1→5)-linked α-L-Araf, (1,3→5)-linked α-L-Araf, (1→6)-linked ß-D-Galp, (1→4)-linked ß-D-Manp, (1,2→5)-linked α-L-Araf, (1→3)-linked ß-L-Rhap, (1, 3→6)-linked ß-D-Manp, (1→3)-linked α-D-GalpA, (1,3→6)-linked ß-D-Galp and (1→6)-linked α-D-Glcp residues. Furthermore, 1.87 nM COP70-3 obviously promoted the differentiation of MC3T3-E1 cells, while 0.94 and 1.87 nM COP70-3 significantly improved the osteogenic mineralization rate. These data indicate that COP70-3 has favorable anti-osteoporosis activity in vitro.

African crocus (Curculigo pilosa) and wonderful kola (Buchholzia coriacea) seeds modulate critical enzymes relevant to erectile dysfunction and oxidative stress.

Background The seeds of African crocus (AC) (Curculigo pilosa) and wonderful kola (WK) (Buchholzia coriacea) are commonly used in folklore medicine in managing erectile dysfunction (ED) without the full understanding of the possible mechanism of actions. This study investigated and compared the effects of aqueous extracts from the seeds of AC and WK on arginase and acetylcholinesterase (AChE) activities and some pro-oxidant [FeSO4 and sodium nitroprusside (SNP)]-induced lipid peroxidation in rat penile homogenate in vitro. Method Aqueous extracts of AC and WK were prepared, and their effects on arginase and AChE activities as well as FeSO4- and SNP-induced lipid peroxidation in rat penile homogenate were assessed. Furthermore, phenolic constituents of the extract were determined using high-performance liquid chromatography coupled with diode-array detector (HPLC-DAD). Results Both extracts exhibited concentration-dependent inhibition on arginase (AC, IC50=0.05 mg/mL; WK, IC50=0.22 mg/mL) and AChE (AC, IC50=0.68 mg/mL; WK, IC50=0.28 mg/mL) activities. The extracts also inhibited FeSO4- and SNP-induced lipid peroxidation in rat penile homogenate. HPLC-DAD analysis revealed the presence of phenolic acids (gallic, caffeic, ellagic and coumaric acids) and flavonoids (catechin, quercetin and apigenin) in AC and WK. AC had higher arginase inhibitory and antioxidative activities but lower AChE inhibitory properties when compared with WK. Conclusions These effects could explain the possible mechanistic actions of the seeds in the management/treatment of ED and could be as a result of individual and/or synergistic effect of the constituent phenolic compounds of the seeds.

Antioxidative and anti-proliferative potential of Curculigo orchioides Gaertn in oxidative stress induced cytotoxicity: In vitro, ex vivo and in silico studies.

Plant phytoconstituents have been a valuable source of clinically important anticancer agents. Antioxidant and anticancerous activity of plant Curculigo orchioides Gaertn were explored In vitro antioxidant activity, antioxidant enzyme activity of oxidatively stressed tissue, and cell culture studies on human cancer cell lines HepG2, HeLa and MCF-7 were carried out. Active plant fractions were subjected to GC-MS analysis and compounds selected on the basis of their abundance were screened in silico with the help of Auto Dock 4.2 tools with pre-selected antioxidant enzymes. Curculigo orchioides Gaertn plant fractions exhibited significant antioxidant activities by virtue of scavenging of free radicals having IC50 value of ethylacetate fraction (EA) for DPPH radical scavenging assay to be 52.93 ±â€¯0.66 µg/ml. Further, antioxidant enzyme defense of mammalian tissue when treated with plant fractions revealed that enzyme concentrations were refurbished which were increased during oxidative stress. MTT assay on cell lines HepG2, HeLa and MCF-7 presented IC50 values of ethylacetate (EA) fraction as 171.23 ±â€¯2.1 µg/ml, 144.80 ±â€¯1.08 µg/ml and 153.51 µg/ml and aqueous ethylacetate (AEA) fraction as 133.44 ±â€¯1.1 µg/ml, 136.50 ±â€¯0.8 µg/ml and 145.09 µg/ml respectively. Further EA and AEA plant fractions down regulated the levels of antiapoptotic Bcl-2 expression and upregulated the expression of apoptotic proteins caspase-3 and caspase-8 through an intrinsic ROS-mediated mitochondrial dysfunction pathway. KEY MESSAGE: Key findings explained that fractions of Curculigo orchioides Gaertn inhibited oxidative stress by increasing the antioxidant enzyme content and have anticancerous potential on cancer cell lines HepG2, HeLa and MCF-7.

A Network Pharmacology Approach to Determine the Active Components and Potential Targets of Curculigo Orchioides in the Treatment of Osteoporosis.

BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components. Targets for the therapeutic actions of CO were obtained from the PharmMapper server database. Pathway enrichment analysis was performed using the Comparative Toxicogenomics Database (CTD). Cytoscape was used to visualize the multiple components-multiple target-multiple pathways-multiple disease network for CO. RESULTS We identified 77 chemical components of CO, of which 32 components could be absorbed in the blood. These potential active components of CO regulated 83 targets and affected 58 pathways. Data analysis showed that the genes for estrogen receptor alpha (ESR1) and beta (ESR2), and the gene for 11 beta-hydroxysteroid dehydrogenase type 1, or cortisone reductase (HSD11B1) were the main targets of CO. Endocrine regulatory factors and factors regulating calcium reabsorption, steroid hormone biosynthesis, and metabolic pathways were related to these main targets and to ten corresponding compounds. CONCLUSIONS The network pharmacology approach used in our study has attempted to explain the mechanisms for the effects of CO in the prevention and treatment of osteoporosis, and provides an alternative approach to the investigation of the effects of this complex compound.

New phenolic glycosides from Curculigo orchioides and their xanthine oxidase inhibitory activities.

Seven new phenolic glycosides including two heterocyclic phenolic derivatives orcinosides I-J (1-2) and five chlorophenolic glycosides curculigines J-N (3-7), together with nineteen known compounds were isolated from the rhizome of Curculigo orchioides. Based on extensive spectroscopic analyses (UV, IR, HRESIMS, 1D and 2D NMR), the structures of the new compounds were identified. Orcinoside I (1) and J (2) displayed xanthine oxidase inhibitory activities with IC50 values 0.25 and 0.62mM respectively.

An O-acetyl-glucomannan from the rhizomes of Curculigo orchioides: Structural characterization and anti-osteoporosis activity in vitro.

Osteoporosis is characterized by a reduction in bone mass and bone mineral density, which weakens the bone. Due to the side effects associated with drugs that are currently used to treat this disease, an increasing number of studies have focused on the research of effective ingredients derived from natural products. In particular, polysaccharides extracted from Chinese herbal medicines have received increasing attention. In this study, we isolated a homogeneous polysaccharide (COP90-1) from the dried rhizomes of Curculigo orchioides, a famous traditional Chinese medicine that is widely used in China, and determined its structure using the combined methods of chemical and spectral analyses. In addition, its effects on the proliferation and differentiation of primary mouse osteoblasts were assessed. The results showed that COP90-1 can effectively promote the proliferation and differentiation of primary osteoblasts in vitro. Additional studies are warranted to study the effects of this compound in vivo.

Total glucosides of Curculigo rhizome to perimenopausal period mice model.

To investigate the effects of total glucosides of Curculigo rhizome (TGC) to perimenopausal period (PMS) mice model. After removed the bilateral ovaries induced the PMS mice model, high, medium and low doses of TGC group were partly given TGC solution 400,200,100mg•kg-1, administered once a day, continuously 21 days. Compared with the model group (MG) mices, each dose of TGC group could significantly improve the activities of mice, increase thymus, uterus, spleen index(TI, UI, SI), the levels of testosterone(T), estradiol (E2), reduce the level of luteinizing hormone (LH), the high dose of TGC group(HD-C) group has the best effects. It prompted that TGC has the effect in treatment of PMS mice model, the HD-C group of TGC has the best effects.

Metabolites of curculigoside in rats and their antiosteoporotic activities in osteoblastic MC3T3-E1 cells.

Curculigoside isolated from Curculiginis Rhizoma exhibits a wide spectrum of bioactivities. In this study, a high performance liquid chromatography/quadrupole time-of- flight tandem mass spectrometry (UHPLC/Q-TOF MS) method was employed to investigate the metabolism of curculigoside in rats. Plasma, bile, urine, feces and 17 tissues were collected from rats after a single PO dose of curculigoside at 100mg/kg and prepared through methanol precipitation. Parent compound and a total of 7 metabolites were detected and identified based on their retention time and fragment ions. Metabolic pathways of curculigoside in rats include hydrolysis, demethylation and glucuronidation. Exposure of major metabolite M2 in plasma and it's antiosteoporotic activity in osteoblastic MC3T3-E1 cells were studied to help understand that curculigoside assimilates less but works more.

Curculigoside augments cell-mediated immune responses in metastatic tumor-bearing animals.

A positive modulation of immune system is necessary for preparing the body to fight against malignant tumor cells. In the present study, the stimulatory effect of Curculigoside on cell-mediated immune response against the metastasis of B16F10 melanoma cells was analyzed in C57BL/6 mice. Curculigoside is a phenolic glucoside present in the plant Curculigo orchioides Gaertn. (Family - Amaryllidaceae). Administration of Curculigoside enhanced the natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity and complement-mediated cytotoxicity in metastatic tumor-bearing animals, when compared to the untreated control animals. The compound was also found to be effective in reducing the levels of proinflammatory cytokines such as TNF-α, IL-1ß, IL-6 and GM-CSF during metastasis. Besides these, levels of TH1 cytokines, such as IL-2 and IFN-γ, were significantly enhanced (p < 0.001) by Curculigoside administration and thereby reduces the metastatic lung colony formation along with an increased lifespan of the experimental animals. These studies provide an evidence for the stimulation of cell-mediated immune responses by Curculigoside against B16F10-induced metastatic tumor progression in experimental animals.

Curculigo orchioides Gaertn Effectively Ameliorates the Uro- and Nephrotoxicities Induced by Cyclophosphamide Administration in Experimental Animals.

Background Curculigo orchioides Gaertn is an ancient medicinal plant (Family: Amaryllidaceae), well known for its immunomodulatory and rejuvenating effects. Cyclophosphamide (CPA) is an alkylating agent widely used for treating a variety of human malignancies, but associated with different toxicities too. Our previous reports regarding the hemoprotective and hepatoprotective effects of the plant against CPA toxicities provide the background for the present study, which is designed to analyze the ameliorative effect of the methanolic extract of C orchioides on the urotoxicity and nephrotoxicity induced by CPA. Methods CPA was administered to male Swiss albino mice at a single dose of 1.5 mmol/kg body weight to induce urotoxicity after 5 days of prophylactic treatment with C orchioides extract (20 mg/kg body weight). Mesna (2-mercaptoethanesulfonate) was used as a control drug. Serum, tissue, and urine levels of kidney function markers and antioxidant levels were checked along with the serum cytokine levels. Results The plant extract was found to be effective in ameliorating the urotoxic and nephrotoxic side effects of CPA. Upregulation of serum interferon-γ and interleukin-2 levels were observed with C orchioides treatment, which was decreased by CPA administration. Besides these, serum tumor necrosis factor-α level was also downregulated by C orchioides treatment. Conclusion Curculigo orchioides was found to be effective against the CPA-induced bladder and renal toxicities by its antioxidant capability and also by regulating the pro-inflammatory cytokine levels.

Phytochemical profile and bioactivity of traditional ayurvedic decoctions and hydro-alcoholic macerations of Boerhaavia diffusa L. and Curculigo orchioides Gaertn.

Decoctions (DECs) and hydro-alcoholic extracts (HEs) prepared from roots of Boerhaavia diffusa L. (Nyctaginaceae) and Curculigo orchioides Gaertn. (Hypoxidaceae) were phytochemically characterised by HPLC-DAD and profiled for their antioxidant, antigenotoxic and cytotoxic activities. B. diffusa DEC was rich in ferulic acid and vanillin, while the HE also contained boeravinone B and eupalitin. Both C. orchioides HE and DEC displayed the main occurrence of orcinol-ß-d-glucoside and curculigoside A. Antioxidant activity was assayed through spectrophotometric DPPH, ABTS and ß-carotene bleaching test, and using (HP)TLC bioautographic strategies. For both crude drugs, HE was the best performing preparation. Properly modified SOS-Chromotest evidenced a 10% inhibition by phytocomplexes against 4-nitroquinoline-N-oxide, and a higher bioactivity for vanillin (36.60 ± 1.68%) and ferulic acid (35.09 ± 1.53%). C. orchioides HE was the preparation which showed higher cytotoxicity against drug-sensitive human T-lymphoblastoid cell line (CCRF-CEM) and multidrug-resistant leukaemia cell line (CEM/ADR5000), and eupalitin was the only pure compound to exhibit an IC50 value.

Enhancement of cancer chemotherapeutic efficacy of cyclophosphamide by Curculigo orchioides Gaertn and its ameliorative effects on cyclophosphamide-induced oxidative stress.

Cyclophosphamide (CTX) is a synthetic antineoplastic drug with severe and life-threatening side effects. Studies in search of protective agents, preferably natural products, that can alleviate these side effects are valuable because they can contribute to improve current chemotherapeutic treatment strategies. Curculigo orchioides Gaertn (family Hypoxidaceae) is well known for its medicinal use in the Indian Ayurvedic system of medicine, and various studies have been reported that proved its immunomodulatory and anti-inflammatory properties. In this study, the tumor reduction capacity of CTX in combination with C orchioides methanolic extract was studied using Dalton's lymphoma ascites-induced solid tumor models. Effect of C orchioides on the reversal of the damage induced by CTX administration (intraperitoneally) was also determined in this study. For this, solid tumor volume, serum cytokine levels, hematolological parameters, intestinal histopathology, and serum and tissue biochemical parameters (Glutathione [GSH], alkaline phosphatase [ALP], glutamate pyruvate transaminase [GPT], lipid peroxidation [LPO]) were analyzed. Immune suppression and increased serum proinflammatory cytokine levels caused by CTX administration (25 mg/kg body weight) were reversed by C orchioides (20 mg/kg body weight). The alcoholic extract enhanced the tumor reduction capacity of CTX and reduced GPT and ALP levels in liver and serum, which were elevated by CTX administration. The LPO level was also lower in the CTX-administered animals when treated with the C orchioides extract. In conclusion, the plant extract when administered in combination with CTX, can result in enhanced anticancer properties; it also ameliorates the toxic side effects of CTX.