Diterpenoid Lactone Research Articles

Anti-inflammatory and antiarthritic properties of Marrubium vulgare aqueous extract in an animal model

This study aimed to investigate the potential anti-inflammatory properties of aqueous extract of Marrubium vulgare (AEMV) using various animal models. Several inflammatory models including xylene-induced ear edoema, carrageenan-induced paw edoema, and Freund’s adjuvant-induced arthritis were employed to evaluate the anti-inflammatory effects of AEMV. LC-MS/MS of AEMV revealed that the major component was Marrubiin, a diterpenoid lactone. AEMV demonstrated significant anti-inflammatory effects in all animal models tested. It effectively reduced ear and paw edoema induced by xylene and carrageenan, respectively. Furthermore, AEMV attenuated arthritis symptoms and hyperalgesia in rats with Freund’s adjuvant-induced arthritis. Biochemical analyzes revealed normalisation of inflammatory markers, including C-reactive protein (CRP) levels, in treated animals. The findings suggest that AEMV possesses promising anti-inflammatory properties, supporting its potential therapeutic application in inflammatory conditions such as arthritis. Further investigations are needed to clarify the underlying mechanisms and optimise dosing regimens for clinical use.

Andrographolide targets EGFR to impede epithelial–mesenchymal transition in human breast cancer cells

Despite the primary surgical treatment for breast cancer patients, malignant invasiveness and metastasis remain threatening factors for women with breast cancer. As chemotherapy yields unsatisfactory results, it prompted us to search for effective natural agents with few side-effects. Although andrographolide (ADGL), a natural diterpenoid lactone isolated from Andrographis paniculata, presents anticancer effects, the molecular mechanism remains unknown. Initially, on comparing the expression of proteins related to epithelial–mesenchymal transition (EMT) between nonmetastatic cancer MCF7 cells and highly metastatic cancer MDA-MB-231 cells, we found that MDA-MB-231 cells exhibit higher protein levels of N-cadherin and vimentin and lower protein levels of E-cadherin when compared to MCF7 cells. Moreover, MDA-MB-231 cells also exhibited higher EGFR expression and activity, higher STAT1 activity and abundant HDAC4 expression. To elucidate whether these proteins are closely associated with EMT, EGFR, STAT1 or HDAC4, the proteins were silenced in MDA-MB-231 breast cancer cells by their specific siRNAs. We found that silencing these proteins reduced EMT, indicating an important role of EGFR, STAT1 and HDAC4 in EMT progression. When we treated MDA-MB-231 cells with ADGL as a potential therapeutic drug, we found that ADGL treatment inhibited cell migration and invasion. Furthermore, it also recovered E-cadherin expression and decreased N-cadherin and vimentin protein levels. ADGL treatment reduced EGFR expression at a lower concentration (1 μg/mL); however, STAT1 activity and HDAC4 expression was reduced by a higher concentration (5 μg/mL) of ADGL. Moreover, we observed that the combined treatment with ADGL and siRNAs against these proteins highly sensitized the MDA-MB-231 cells to apoptosis compared to that with ADGL and control siRNA. Collectively, our results suggest that ADGL targets EGFR, thereby inhibiting EMT in human breast cancer cells.

Nitrogen Sources Reprogram Carbon and Nitrogen Metabolism to Promote Andrographolide Biosynthesis in Andrographis paniculata (Burm.f.) Nees Seedlings.

Carbon (C) and nitrogen (N) metabolisms participate in N source-regulated secondary metabolism in medicinal plants, but the specific mechanisms involved remain to be investigated. By using nitrate (NN), ammonium (AN), urea (UN), and glycine (GN), respectively, as sole N sources, we found that N sources remarkably affected the contents of diterpenoid lactone components along with C and N metabolisms reprograming in Andrographis paniculata, as compared to NN, the other three N sources raised the levels of 14-deoxyandrographolide, andrographolide, dehydroandrographolide (except UN), and neoandrographolide (except AN) with a prominent accumulation of farnesyl pyrophosphate (FPP). These N sources also raised the photosynthetic rate and the levels of fructose and/or sucrose but reduced the activities of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoenolpyruvate carboxylase (PEPC) and pyruvate dehydrogenase (PDH). Conversely, phosphoenolpyruvate carboxykinase (PEPCK) and malate enzyme (ME) activities were upregulated. Simultaneously, citrate, cis-aconitate and isocitrate levels declined, and N assimilation was inhibited. These results indicated that AN, UN and GN reduced the metabolic flow of carbohydrates from glycolysis into the TCA cycle and downstream N assimilation. Furthermore, they enhanced arginine and GABA metabolism, which increased C replenishment of the TCA cycle, and increased ethylene and salicylic acid (SA) levels. Thus, we proposed that the N sources reprogrammed C and N metabolism, attenuating the competition of N assimilation for C, and promoting the synthesis and accumulation of andrographolide through plant hormone signaling. To obtain a higher production of andrographolide in A. paniculata, AN fertilizer is recommended in its N management.

Andrographolide attenuates sepsis-induced acute kidney injury by inhibiting ferroptosis through the Nrf2/FSP1 pathway

Sepsis is a systemic inflammatory response syndrome caused by infection, which causes renal dysfunction known as sepsis-associated acute kidney injury (S-AKI). Ferroptosis is a form of lipid peroxidation dependent on iron and reactive oxygen species that differs from other forms of programmed cell death at the morphological and biochemical levels. Andrographolide (AG), a natural diterpenoid lactone compound extracted from Andrographis paniculata, has been shown to have therapeutic effects in kidney disease. In this study, we investigated the novel mechanism by which AG attenuates septic acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells (HK-2) through the Nrf2/FSP1 pathway. Cecum ligation and puncture (CLP)-induced septic rats and lipopolysaccharide (LPS)-induced HK-2 cells were used for in vivo and in vitro experiments. Firstly, in septic rats and HK-2 cells, AG effectively decreased the levels of kidney injury indicators, including blood creatinine, urea nitrogen, and markers of kidney injury such as neutrophil gelatinase-associated lipid transport protein and kidney injury molecule-1 (KIM-1). In addition, AG prevented ferroptotosis, by avoiding the accumulation of iron and lipid peroxidation, and an increase in SLC7A11 and GPX4 in AG-treated HK-2 cells. Furthermore, AG attenuated mitochondrial damage, including mitochondrial swelling, outer membrane rupture, and a reduction in mitochondrial cristae in LPS-treated HK-2 cells. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly inhibited LPS-induced ferroptosis in HK-2 cells. Importantly, our results confirm that Nrf2/FSP1 is an important pathway for ferroptosis resistance. Nrf2 siRNA hindered the effect of AG in attenuating acute kidney injury and inhibiting ferroptosis. These findings demonstrate that Nrf2/FSP1-mediated HK-2 ferroptosis is associated with AG, alleviates septic acute kidney injury, and indicates a novel avenue for therapeutic interventions in the treatment of acute kidney injury in sepsis.

In silico docking study of selected compounds for its hepatoprotective activity

Liver fibrosis is a condition characterized by the excessive accumulation of scar tissue in the liver. It is typically caused by chronic liver diseases, such as chronic viral hepatitis (e.g., hepatitis B and C), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis, and certain genetic conditions. Ephrin receptor A2 (EphA2) is identified as potential anti-inflammatory target which influences inflammatory process and immune response, impacting the recruitment and activation of immune cells and as a host cofactor for Hepatitis C Virus (HCV) entry. Andrographolide a diterpenoid lactone, Scoulerine a natural alkaloid possess anti-inflammatory activity. The present work was done to evaluate anti-inflammatory activity of andrographolide and scoulerine using software Autodock 4.2. Phyto-constituents were fetched from the PubChem database. 3D structure of EphA2 were downloaded from Protein Data Bank (PDB). Among two phyto compounds, andrographolide had highest binding energy of -7.58 which is a clear evident of potential anti-inflammatory activity and prevent hepatic fibrosis. The active site of the target protein was predicted by using CASTP (Computed atlas of surface topography of proteins). Protein ligand interaction information is obtained by Protein ligand interaction profiler.

Nitrogen-containing andrographolide derivatives with multidrug resistance reversal effects in cancer cells.

Multidrug resistance (MDR) remains a challenging issue in cancer treatment. Aiming at finding anticancer agents to overcome MDR, the triacetyl derivative (2) of the labdane diterpenoid lactone andrographolide (1) underwent the Michael-type addition reaction followed by elimination, yielding twenty-three new derivatives, bearing nitrogen-containing substituents (3-25). Their structures were assigned, mainly, by 1D and 2D NMR experiments. The MDR reversal potential of compounds 1-25 was assessed, by functional and chemosensitivity assays, using resistant human ABCB1-gene transfected L5178Y mouse lymphoma cells as a model. Several derivatives exhibited remarkable P-glycoprotein (P-gp) inhibitory ability. Compounds 13 and 20, bearing thiosemicarbazide moieties, were the most active exhibiting a strong MDR reversal effect at 2 μM. Some compounds showed selectivity towards the resistant cells, with compound 5 exhibiting a collateral sensitivity effect associated with significant antiproliferative activity (IC50 = 5.47 ± 0.22 μM). Moreover, all selected compounds displayed synergistic interaction with doxorubicin, with compound 3 being the most active. In the ATPase assay, selected compounds exhibited characteristics of P-gp inhibitors.

Unveiling Various Facades of Tinospora cordifolia Stem in Food: Medicinal and Nutraceutical Aspects.

Natural products with curative properties are gaining immense popularity in scientific and food research, possessing no side effects in contrast to other drugs. Guduchi, or Tinospora cordifolia, belongs to the menispermaceae family of universal drugs used to treat various diseases in traditional Indian literature. It has received attention in recent decades because of its utilization in folklore medicine for treating several disorders. Lately, the findings of active phytoconstituents present in herbal plants and their pharmacological function in disease treatment and control have stimulated interest in plants around the world. Guduchi is ethnobotanically used for jaundice, diabetes, urinary problems, stomachaches, prolonged diarrhea, skin ailments, and dysentery. The treatment with Guduchi extracts was accredited to phytochemical constituents, which include glycosides, alkaloids, steroids, and diterpenoid lactones. This review places emphasis on providing in-depth information on the budding applications of herbal medicine in the advancement of functional foods and nutraceuticals to natural product researchers.

Simultaneous Quantification of Major Bio‐Active Diterpenoid Lactones and Flavonoids in Andrographis paniculata (Burm. F.) Nees: LC‐ESI‐MS/MS Method Validation and Uncertainty Determination

AbstractDiterpenoid lactones and flavonoids are major bio‐active compounds of therapeutically important medicinal herb Andrographis paniculata (Burm.F.) Nees. The lack of a validated protocol for quality assurance of raw herbs is a significant issue for its wider use. A validated LC‐ESI‐MS/MS method developed using MRM mode for simultaneous determination of five diterpenoid lactones (andrographolide, neoandrographolide, andrograpanin, 14‐deoxy‐11,12‐didehydroandrographolide and andrographiside) along with two flavonoids (7‐O‐methylwogonin and apigenin). Chromatographic separation of seven analytes was achieved within 14 minutes in Alltima column (100×4.6 mm, 3 μm) using gradient elution. The developed method was accurate (97.77 to 101.17 %; recovery), precise (intra‐day and inter‐day %RSD of 0.22–2.19 and 1.01–3.68, respectively) and linear (R2 >0.99). To meet the regulatory obligation, uncertainty associated with the measurement was also evaluated by using different validation parameters. Developed method was successfully employed in analysing the analytes quality in different solvent extracts. Total diterpenoid lactones and flavonoids (DTLF) content was recorded highest in methanol extract (45.47 μg g−1) followed by ethanol (39.23 μg g−1) and lowermost content found in petroleum ether extract (0.38 μg g−1) in triplicate samples. Since the method is simple, rapid, sensitive, and accurate, it has potential role for quality evaluation of A. paniculata and its derived formulation.

Retracted: Adoption of Magnetic Resonance Image Features under Segmentation Algorithm in Effect Evaluation of Ginkgo Diterpenoid Lactone Glucamine Injection in Treatment of Cerebral Infarction.

[This retracts the article DOI: 10.1155/2022/4558702.].

The Development of Germination Tests and Breaking Dormancy Techniques of Bitter Seeds (Andrographis paniculata (Burm. f.) Wall. ex Nees)

Bitter seed (Andrographis paniculata (Burm. f.) Wall. ex Nees) is a medicinal species used in phyto pharmacy and known as ‘the king of bitterness’. Bitter seeds contain andrographolide,
 a diterpenoid lactone which is widely used in Indian medicine for snake bites and for the treatment of hepatitis. The research was conducted at the Seed Management Unit experimental field of the Indonesian Spice and Medicinal Plants Research Institute (IMACRI) and at the Seed Quality Testing Laboratory of IPB University, Indonesia, from January until May 2021. The objectives of the study is to determine the best germination test and effective breaking dormancy techniques to increase the germination percentage of bitter seeds. The study was arranged in a completely randomized design with two-factors. The first factor was seed treatments, i.e., control/untreated, chemical scarification with 5% H2SO4 for 10 minutes, and 5% H2SO4 followed by a 100 ppm GA3 soaking treatment. The second factor conducted was germination test methods according to International Seed Testing Association, i.e., germinating the seeds on the top of paper and in pleated paper. Our study demonstrated that seed treatment with H2SO4 can break seed dormancy and speed up seed germination. Bitter seed germination on the pleated paper was higher than with the top-of-paper method. Bitter seed germination with the top-of-paper method was at 65 DAS and the final germination was at 80 days after sowing (DAS), and the final germination was 55.2%. With the pleated paper method, the seeds germinated at 30 DAS and the final germination was at 70 DAS, and the final the germination of 59.2%.

Toxicological mechanism of triptolide-induced liver injury: Caspase3-GSDME-mediated pyroptosis of Kupffer cell

AimTriptolide (TRI) is an active diterpenoid lactone compound isolated from Tripterygium wilfordii,We focused on investigating the effect and mechanism of Triptolide (TRI) on liver injury. MethodsThe toxic dose (LD50 = 100 μM) of TRI on liver Kupffer cells was explored, and network pharmacological analysis was performed to identify Caspase-3 as the target of TRI-induced liver injury. Regarding the pyroptosis research, we examined the level of TRI-induced pyroptosis in Kupffer cells, including inflammatory cytokine detection, protein assay, microscopic cell observation and LDH toxicity test. The effect of TRI on pyroptosis was assessed after knocking out GSDMD, GSDME and Caspase-3 in cells, respectively. We also investigated the liver injury-inducing action of TRI at the animal level. ResultsOur experimental results were consistent with those predicted by network pharmacology, indicating that TRI could bind to Caspase-3-VAL27 site to promote the cleavage of Caspase-3, and Cleaved-Caspase-3 induced pyroptosis of Kupffer cells through GSDME cleavage. GSDMD was not involved in TRI’s action. TRI could promote Kupffer cell pyroptosis, elevate the inflammatory cytokine levels, and facilitate the expressions of N-GSDME and Cleaved-Capase 3. After the mutation of VAL27, TRI could not bind to Caspase-3. Animal-level results showed that TRI could induce liver injury in mice, while Caspase-3 knockout or Caspase-3 inhibitors could antagonize the action of TRI. ConclusionWe find that the TRI-induced liver injury occurs primarily through the Caspase-3-GSDME pyroptosis signal. TRI can promote Caspase − 3 maturation and regulate kupffer cell pyroptosis. The present findings offer a new idea for the safe use of TRI.

Seco-pimarane diterpenoids and androstane steroids from an endophytic Nodulisporium fungus derived from Cyclosorus parasiticus

Five previously undescribed specialized metabolites, including three 9,11-seco-pimarane diterpenoids, nodulisporenones A–C, and two androstane steroids, nodulisporisterones A and B, together with previously described ergosterol derivatives, dankasterone A and demethylincisterol A3, were isolated from solid cultures of the endophytic fungus Nodulisporium sp. SC-J597. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and theoretical calculations of electronic circular dichroism spectra. Among them, nodulisporenones A and B are the first examples of seco-pimarane diterpenoids that is cyclized to form an unprecedented diterpenoid lactone scaffold and nodulisporisterones A and B represent the first normal C19 androstane steroids of fungal origin. Nodulisporisterone B exhibited potent inhibitory effect on the production of NO in LPS-stimulated RAW264.7 macrophages (IC50 = 2.95 μM). This compound, together with the two known ergosterol derivatives, also displayed cytotoxicity against A549, HeLa, HepG2 and MCF-7 cancer cell lines with IC50 values of 5.2–16.9 μM.

Screening of Prospective Antiallergic Compound as FcεRI Inhibitors and Its Antiallergic Efficacy Through Immunoinformatics Approaches.

The occurrence of allergy, a type I hypersensitivity reaction, is rising exponentially all over the world. Sometimes, allergy proves to be fatal for atopic patients, due to the occurrence of anaphylaxis. This study is aimed to find an anti-allergic agent that can inhibit the binding of IgE to Human High Affinity IgE Receptor (FCεRI), thereby preventing the degranulation of mast cells. A considerable number of potential anti-allergic compounds were assessed for their inhibitory strength through ADMET studies. AUTODOCK was used for estimating the binding energy between anti-allergic compounds and FCεRI, along with the interacting amino acids. The docked pose showing favorable binding energy was subjected to molecular dynamics simulation study. Marrubiin, a diterpenoid lactone from Lamiaceae, and epicatechin-3-gallate appears to be effective in blocking the Human High Affinity IgE Receptor (FCεRI). This in-silico study proposes the use of marrubiin and epicatechin-3-gallate, in the downregulation of allergic responses. Due to the better inhibition constant, future direction of this study is to analyze the safety and efficacy of marrubiin in anti-allergic activities through in-vivo clinical human trials.

Preparation, characterization, and safety assessment of statistical optimized probiotic supplemented herbal wine from Tinospora cordifolia.

Evidently proven medicinal benefits of Tinospora cordifolia and the growing demand of functional foods have created scientific interest in the functional beverage. Therefore, an attempt was made to prepare probiotic Lactiplantibacillus pentosus GSSK2 supplemented herbal wine having the benefits of both phytochemical and probiotic. Experimentally, fermentation of Tinospora cordifolia stem was found to be the most effective with ammonium dihydrogen phosphate, potassium phosphate, magnesium sulfate, isoleucine, and thiamine that yielded maximum ethanol (6.8 to 10%), total phenol (419 to 791.5µg/ml), and antioxidants capacity (98.2 to 160.4µmol/ml) after optimizing physical parameters, i.e., 20° Brix total soluble solid, pH 4.5, temperature 30°C, and 10% (v/v) inoculum. Further, prepared herbal wine was supplemented separately with seven different probiotic strains and among these Lactiplantibacillus pentosus GSSK2 had the highest 88.6% survival rate compared with other probiotics and was safe showing 100% survivability of HEK-293 and THP-1 cells. Both herbal- and probiotic-supplemented herbal wine showed the antimicrobial potential against Gram-positive and Gram-negative bacteria as probiotic-supplemented herbal wine had 19-21mm inhibition zone compared with 18-19mm with herbal wine. LC-MS analysis of the probiotic-supplemented herbal wine revealed the presence of various phytochemicals such as alkaloids, diterpenoid lactone, glycoside, steroids having anti-bacterial, anti-oxidant, and anti-inflammatory potential. This is the first ever such study to demonstrate the antibacterial, antioxidant potential and safety of probiotic supplemented herbal wine in vitro.

DNA damage and up-regulation of PARP-1 induced by columbin in vitro and in vivo

Columbin (CLB) is the most abundant (>1.0%) furan-containing diterpenoid lactone in herbal medicine Tinospora sagittate (Oliv.) Gagnep. The furano-terpenoid was found to be hepatotoxic, but the exact mechanisms remain unknown. The present study demonstrated that administration of CLB at 50 mg/kg induced hepatotoxicity, DNA damage and up-regulation of PARP-1 in vivo. Exposure to CLB (10 μM) induced GSH depletion, over-production of ROS, DNA damage, up-regulation of PARP-1 and cell death in cultured mouse primary hepatocytes in vitro. Co-treatment of mouse primary hepatocytes with ketoconazole (10 μM) or glutathione ethyl ester (200 μM) attenuated the GSH depletion, over-production of ROS, DNA damage, up-regulation of PARP-1, and cell death induced by CLB, while co-exposure to L-buthionine sulfoximine (BSO, 1000 μM) intensified such adverse effects resulting from CLB exposure. These results suggest that the metabolic activation of CLB by CYP3A resulted in the depletion of GSH and increase of ROS formation. The resultant over-production of ROS subsequently disrupted the DNA integrity and up-regulated the expression of PARP-1 in response to DNA damage, and ROS-induced DNA damage was involved in the hepatotoxicity of CLB.

Andrographolide suppresses aerobic glycolysis and induces apoptotic cell death by inhibiting pyruvate dehydrogenase kinase 1 expression.

Metabolic disorder is a major characteristic of cancer cells, and controlling genes involved in metabolic shifts can be an effective strategy for cancer treatment. Andrographolide (AG), a diterpenoid lactone, is widely recognized as a natural anticancer drug due to its ability to inhibit cancer growth. The present study aimed to investigate the mechanism underlying the mitochondrial‑mediated anticancer effect of AG by inhibiting pyruvate dehydrogenase kinase 1 (PDK1) expression in lung cancer cells. Cells were treated with AG and PDK1 mRNA and protein expression was determined using reverse transcription‑quantitative PCR and western blotting, respectively. As a result, AG significantly inhibited the viability of human lung cancer cells and suppressed aerobic glycolysis by decreasing lactate generation. AG further decreased the PDK1 protein and mRNA levels in a dose‑dependent manner. AG‑induced cell death was assessed by flow cytometry and fluorescence microscopy. AG induced apoptotic cell death that was associated with the cleavage of poly (ADP ribose) polymerase, activation of caspase‑3, and mitochondrial damage, which was associated with an increase in reactive oxygen species and loss of mitochondrial membrane potential. AG‑induced cell death was partially suppressed via PDK1 overexpression in lung cancer cells. Therefore, the anticancer effects of AG on human lung cancer cells may negatively regulate the expression of PDK1.

Preliminary Larvicidal Potential of Andrographis Echioides against Dengue Vector Aedes aegypti Larvae

Aim/Background: The present study was conducted to assess the larvicidal potential of Andrographis echiodies against the dengue vector Aedes aegypti larvae. Alcoholic leaf extract of Andrographis echiodies was studied at 500, 250, 125, 62.5, 31.25, and 15.625 ppm concentrations against third-instar larvae of Aedes aegypti. Materials and Methods: 100 larvae of Aedes aegypti mosquitoes were exposed to each concentration of both ethanolic and methanolic crude extract of Andrographis echiodies in a volume of 100ml. To minimize the error five replicates were employed with respective diluted alcoholic solutions as control. The percentage mortality of larvae at different concentrations of both alcoholic extracts and control were recorded after 24 hr and 48 hr of constant exposure followed by LC50 and LC90 determined. Results: The effective and highest coefficient of determination (R2) was calculated using regression analysis. The effective and highest coefficient of determination (R2) was 0.88 in 24 hr of exposure of larvae in methanolic leaf extract of Andrographis echioides. Similarly, the effective and highest coefficient of determination (R2) was 0.94 in 24 hr of exposure larvae in ethanolic leaf extract of Andrographis echioides. Conclusion: From the result it was concluded that both methanolic and ethanolic leaf extract of Andrographis echioides exhibited larvicidal activity against the dengue vector Aedes aegypti larvae and it may be due to its secondary metabolite diterpenoid lactone. Further studies may be needed to expose its exact mechanism of action.

Tinospora Cordifolia – A Review

Traditional systems of medicine such as Ayurvedic, Uninai, Siddha and Homeopathy (AYUSH) have been practice in a great account. There is a growing demand for plant based medicines, health products, pharmaceuticals food supplements, cosmetics etc. This plant belongs to the family Menispermaceae. A variety of constituents have been isolated from different parts of T. cordifolia. They belong to different classes such as alkaloids, diterpenoid lactones, steroids, glycosides, aliphatic compounds and polysaccharides. A review of chemical constitutes present in various parts of Tinospora cordifolia and their pharmacological actions is given in the present article. The study is an attempt to review the status of phytochemical and pharmacological profile of Tinospora cordifolia. Review articles is presented to comply all the updated information on its phytochemical and pharmacological activities, which were performed by widely different methods. The notable medicinal properties are anti-diabetic, anti-spasmodic, anti-malarial, anti-inflammatory, anti-arthritic, anti-oxidant, anti-allergic, anti-stress, anti-leprotic, hepatoprotective, immunmodulatory, & anti-neoplastic activities.etc. This review is aimed at summarizing the published knowledge of the traditional uses, botanical description, pharmacological profile and phytochemical reports of Tinospora cordifolia to reveal its therapeutic potentials and scope for future researches. Aim of this article is to give fast review about Tinospora cordifolia.

New 3,4-seco-3,19-Dinor- and Spongian-Based Diterpenoid Lactones from the Marine Sponge Spongia sp.

Continuing chemical investigation of the Red Sea sponge Spongia sp. led to the isolation of four new 3,4-seco-3,19-dinorspongian diterpenoid lactones, secodinorspongins A-D (1-4), along with a classical spongian diterpenoid lactone, sponginolide (5). The chemical structures, including the absolute configurations of these compounds, were elucidated using the extensive spectroscopic study composed of 1D and 2D NMR data analyses, and a comparison between calculated-electronic-circular-dichroism (ECD) and experimental-circular-dichroism (CD) spectra. A plausible biosynthetic pathway of 1-4 was also proposed. Furthermore, the cytotoxicity, antibacterial and anti-inflammatory activities of 1-5 were evaluated. Compound 1 was found to exhibit inhibitory activity against the growth of Staphylococcus aureus (S. aureus), and 4 and 5 exhibited suppression of superoxide-anion generation and elastase release in fMLF/CB-induced human neutrophils.

Discovery of two ent-atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana.

Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh2(OCOCF3)4-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC50 = 2.13 ± 0.06 μM and Ki = 0.058 μM), which was five times stronger than that of the positive control (rivastigmine, IC50 = 12.46 ± 0.82 μM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism.