Traditional Uses, Chemical Constituents and Pharmacological Activities of the Toona sinensis Plant.

Toona sinensis (A. Juss.) Roem., which is widely distributed in China, is a homologous plant resource of medicine and food. The leaves, seeds, barks, buds and pericarps of T. sinensis can be used as medicine with traditional efficacy. Due to its extensive use in traditional medicine in the ancient world, the T. sinensis plant has significant development potential. In this review, 206 compounds, including triterpenoids (1-133), sesquiterpenoids (134-135), diterpenoids (136-142), sterols (143-147), phenols (148-167), flavonoids (168-186), phenylpropanoids (187-192) and others (193-206), are isolated from the T. sinensis plant. The mass spectrum cracking laws of representative compounds (64, 128, 129, 154-156, 175, 177, 179 and 183) are reviewed, which are conducive to the discovery of novel active substances. Modern pharmacological studies have shown that T. sinensis extracts and their compounds have antidiabetic, antidiabetic nephropathy, antioxidant, anti-inflammatory, antitumor, hepatoprotective, antiviral, antibacterial, immunopotentiation and other biological activities. The traditional uses, chemical constituents, compound cracking laws and pharmacological activities of different parts of T. sinensis are reviewed, laying the foundation for improving the development and utilization of its medicinal value.

Physicochemical properties and solution conformation of polysaccharides from Toona sinensis (A. Juss) Roem leaves.

In this study, two polysaccharide fractions (TSP-1 and TSP-2) were isolated from Toona sinensis leaves. The physicochemical properties and solution conformations of TSP-1 and TSP-2 were investigated. DSC and TG results showed that TSP-1 and TSP-2 had thermal stability. The intrinsic viscosities of TSP-1 and TSP-2 solutions were 11.42 and 6.13 mL/g, respectively. Rheological results showed that the viscosities of TSP-1 and TSP-2 solutions were affected by polysaccharide concentration, Ca2+ and extreme pH. Furthermore, TSP-1 exhibited a weak gel behavior at the concentrations of 0.5 %-2.0 %, while TSP-2 showed a weak gel behavior at the concentration of 2 %. HPSEC-MALLS analysis revealed that the Rg values of TSP-1 and TSP-2 were 96.8 nm and 56.2 nm, respectively. Conformation analysis indicated that TSP-1 behaved as a sphere, while TSP-2 behaved like a rigid rod. These results suggest that TSP-1 and TSP-2 can be used as additives in food, pharmaceutical and cosmetic industries.

Brassinolide Soaking Reduced Nitrite Content and Extended Color Change and Storage Time of Toona sinensis Bud during Low Temperature and Near Freezing-Point Temperature Storage.

Low temperatures are often used to preserve fruits and vegetables. However, low-temperature storage also causes problems, such as chilling injury, nitrite accumulation, and browning aggravation in plants. This study investigated the effects of brassinolide (BR,1.0 mg L-1) solution soaking, storage temperatures (-2 ± 0.5 °C, 4 ± 0.5 °C, and 20 ± 1 °C), and their combinations on nitrite content, color change, and quality of stored Toona sinensis bud. The results showed that low temperature (LT, 4 ± 0.5 °C) and near freezing-point temperature (NFPT, -2 ± 0.5 °C) storage effectively inhibited the decay of T. sinensis bud compared to room temperature (20 ± 1 °C, the control). The combined treatments of BR with LT or NFPT reduced nitrite content and maintained the color and the contents of vitamin C, carotenoids, saponins, ß-sitosterol, polyphenol, anthocyanin, flavonoids, and alkaloids in T. sinensis bud. BR soaking delayed the occurrence of chilling injury during NFPT storage. Meanwhile, BR soaking enhanced the DPPH radical scavenging activity, ABTS activity, and FRAP content by increasing SOD and POD activity and the contents of proline, soluble, and glutathione, thus decreasing MDA and hydrogen peroxide content and the rate of superoxide radical production in T. sinensis bud during NFPT storage. This study provides a valuable strategy for postharvest T. sinensis bud in LT and NFPT storage. BR soaking extended the shelf life during LT storage and maintained a better appearance and nutritional quality during NFPT storage.

Terpenoids from the Seeds of Toona sinensis and Their Ability to Attenuate High Glucose-Induced Oxidative Stress and Inflammation in Rat Glomerular Mesangial Cells.

Toona sinensis (A. Juss.) Roem is an edible medicinal plant that belongs to the genus Toona within the Meliaceae family. It has been confirmed to display a wide variety of biological activities. During our continuous search for active constituents from the seeds of T. sinensis, two new acyclic diterpenoids (1-2), together with five known limonoid-type triterpenoids (3-7), five known apotirucallane-type triterpenoids (8-12), and three known cycloartane-type triterpenoids (13-15), were isolated and characterized. Their structures were identified based on extensive spectroscopic experiments, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectra (HR-ESI-MS), and electronic circular dichroism (ECD), as well as the comparison with those reported in the literature. We compared these findings to those reported in the literature. Compounds 5, 8, and 13-14 were isolated from the genus Toona, and compounds 11 and 15 were obtained from T. sinensis for the first time. The antidiabetic nephropathy effects of isolated compounds against high glucose-induced oxidative stress and inflammation in rat glomerular mesangial cells (GMCs) were assessed in vitro. The results showed that new compounds 1 and 2 could significantly increase the levels of Nrf-2/HO-1 and reduce the levels of NF-κB, TNF-α, and IL-6 at concentrations of 30 µM. These results suggest that compounds 1 and 2 might prevent the occurrence and development of diabetic nephropathy (DN) and facilitate the research and development of new antioxidant and anti-inflammatory drugs suitable for the prevention and treatment of DN.

Identification of the novel natural product inhibitors of SHP2 from the plant Toona sinensis: In vitro and in silico study.

In this study, we tested the inhibitory activity of 45 natural products extracted from the plant Toona sinensis on SHP2 protein, and identified four natural product inhibitors. The natural product 1,2,3,6-Tetragalloylglucose (A-1) was first reported as a competitive inhibitor of SHP2, with an IC50 value of 0.20 ± 0.029 µM and the selectivity of 1.8-fold and 4.35-fold to high homologous proteins SHP1 and PTP1B, respectively. Compound A-1 also showed high inhibitory activity on SHP2-E76K and SHP2-E76A mutants, with IC50 values of 0.95 ± 0.21 µM and 0.29 ± 0.045 µM, respectively. Cell viability assay showed that compound A-1 could inhibit the proliferation of a variety of cancer cells. Apoptosis assay showed that compound A-1 could effectively induce apoptosis of KRASG12C-mut NCI-H23 and KRASG12S-mut A549 cells. Western blot assay showed that compound A-1 could down regulate the phosphorylation levels of Erk1/2 and Akt in NCI-H23 and A549 cells. Molecular docking showed that compound A-1 could effectively dock to the catalytic active region of SHP2. Molecular dynamics simulation explored the effect of compound A-1 on SHP2, revealing the deep-seated binding mechanism. This study would provide valuable clues for the development of SHP2 and its mutant inhibitors.

Membrane reactor based synthesis of biodiesel from Toona ciliata seed oil using barium oxide nano catalyst.

Membrane technology has been embraced as a feasible and promising substitute to the traditional technologies employed for biodiesel synthesis which are energy and time consuming. It needs less energy, has high stability, is environmentally friendly, and is simple to operate and control. Therefore, in our current study membrane technology was employed to synthesize biodiesel from Toona ciliate novel and non-edible seed oil. Since Toona ciliata has affluent oil content (33.8%) and is effortlessly and extensively available. In fact, we intended to scrutinize the effects of green synthesized barium oxide nanoparticles for one step transesterification of biodiesel production using membrane technology followed by characterization of prepared catalyst via innovative techniques. Optimal yield of biodiesel attained was 94% at 90 °C for 150 min with methanol to oil molar ratio of 9:1 and amount of about 0.39 wt %. Quantitative analysis of synthesized Toona ciliata oil biodiesel was carried out by advance techniques of Gas chromatography mass spectrometry (GC-MS), Fourier-transform infrared (FTIR) spectroscopy and Nuclear magnetic resonance (NMR) which authorize the synthesis of fatty acid methyl ester compounds using oil from Toona ciliata seeds. Values of Toona ciliata fuel properties for instance flash point (70°C), density (0.89 kg/m3), viscosity (5.25 mm2/s), cloud point (-8°C) and pour point (-11°C) met the specifications of international standards i. e American (ASTM D-6751), European (EN-14214) and China (GB/T 20,828). Subsequently, it is concluded that membrane technology is environmentally friendly and efficient technique for mass-production of sustainable biodiesel using green nano catalyst of barium oxide.

Biomediated synthesis, characterization, and biological applications of nickel oxide nanoparticles derived from Toona ciliata, Ficus carica and Pinus roxburghii.

Biomediated ecofriendly method for the synthesis of nickel oxide nanoparticles using plants extracts (Toona ciliata, Ficus carica and Pinus roxburghii) has been reported. The nanoparticles so obtained were characterized by various techniques such as ultraviolet-visible, powder X-ray diffraction, Fourier transform infrared spectroscopy, attenuated total reflectance spectroscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, thermogravimetric analysis and fluorescence spectroscopy. Formation of nickel oxide nanoparticles was confirmed by Fourier transform infrared spectroscopy and X-ray diffraction where the former technique ascertains the formation of bond between nickel and oxygen. The nickel oxide nanoparticles were found to be crystalline cubic face centered and show intense photoluminescence emission at 416, 414 and 413 nm, respectively. The antibacterial activity was studied against gram positive and gram negative bacterial species by agar well diffusion method. The nickel oxide nanoparticles show better activity against some bacterial strains with reference to the standard drugs Ciprofloxacin and Gentamicin. The anthelmintic activity against Pheretima posthuma of nanomaterials obtained from Pinus roxburghii was found to be greater than that derived from Toona ciliata and Ficus carica using the standard drug Albendazole. This method takes the advantage of the sustainable and economic approach for the synthesis of metal oxide nanoparticles.

Induction of mitochondrial-dependent apoptosis by essential oil of Toona sinensis root through Akt, mTOR and NF-κB signalling pathways in human renal cell carcinoma cells.

Natural products have long been considered as a kind of complementary medicine. In this study, we investigate the apoptotic effect of essential oils of Toona sinensis roots (TSR) on human clear cell renal cell carcinomas (ccRCC). The sesquiterpene content of TSR essential oil was determined via GC/MS analysis. TSR decreased ccRCC cell viabilities, inducing ROS generation and reduction of the mitochondrial membrane potential. Moreover, TSR inhibited Bcl-2 and Hsp90 expression but increased PARP-1 cleavage and cytochrome c release. Akt, mTOR and NF-κB phosphorylation and HIF-α expression were all inhibited, which likely contributed to the anti-proliferative and anti-adhesive effects of TSR.

Toonamicrocarpavarin, a new tirucallane-type triterpenoid from Toona Ciliata.

Toonamicrocarpavarin (1), a new tirucallane-type triterpenoid, along with eight known ones, piscidinol A (2), toonaciliatavarin E (3), toonayunnanin A (4), 7-acetyneotrichilenone (5), hispidol A (6), odoratone (7), phellochin (8), toonaciliatavarin D (9), were isolated from T. ciliata. Their structures were identified on the basis of ESIMS, HREIMS and 1 D/2D NMR analysis. The cytotoxic activity of the new compound was also evaluated. All compounds were obtained from T. ciliata for the first time, which plays an important role in chemotaxonomy of the plant T. ciliata.

Limonoids from the Fresh Young Leaves and Buds of Toona sinensis and Their Potential Neuroprotective Effects.

Toona sinensis, popularly known as Chinese toon or Chinese mahogany, is a perennial deciduous arbor belonging to the genus Toona in the Meliaceae family, which is widely distributed and cultivated in eastern and southeastern Asia. Its fresh young leaves and buds have been consumed as a very popular nutritious vegetable in China and confirmed to display a wide variety of biological activities. To investigate the chemical constituents and their potential health benefits from the fresh young leaves and buds of T. sinensis, a phytochemical study on its fresh young leaves and buds was therefore undertaken. In our current investigation, 16 limonoids (1-16), including four new limonoids, toonasinenoids A-D (1-4), and a new naturally occurring limonoid, toonasinenoid E (5), were isolated and characterized from the fresh young leaves and buds of T. sinensis. The chemical structures and absolute configurations of limonoids 1-5 were elucidated by comprehensive spectroscopic data analyses. All known limonoids (6-16) were identified via comparing their experimental spectral data containing mass spectrometry data, 1H and 13C nuclear magnetic resonance data, and optical rotation values to the data reported in the literature. All known limonoids (6-16) were isolated from T. sinensis for the first time. Furthermore, the neuroprotective effects of all isolated limonoids 1-16 against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells were assessed in vitro. Limonoids 1-16 exhibited notable neuroprotective activities, with EC50 values in the range from 0.27 ± 0.03 to 17.28 ± 0.16 µM. These results suggest that regular consumption of the fresh young leaves and buds of T. sinensis might prevent the occurrence and development of Parkinson's disease (PD). Moreover, the isolation and characterization of these limonoids that exhibit notable neuroprotective activities from the fresh young leaves and buds of T. sinensis could be very significant for researching and developing new neuroprotective drugs used for the prevention and treatment of PD.

The Leaf Extracts of Toona sinensis and Fermented Culture Broths of Antrodia camphorata Synergistically Cause Apoptotic Cell Death in Promyelocytic Leukemia Cells.

Toona sinensis is a common edible vegetable that is used in certain Chinese dishes and has importance in folk medicine. The leaf extracts of T sinensis possess and exhibit anticancer efficacy against various cancer cell types. In Taiwanese folklore, Antrodia camphorata, also known as "Niu-Cheng-Zi," is used in traditional medicine to treat various illnesses. Its fruit and mycelium possess various potent antiproliferative properties. Two studies from our group have reported that T sinensis or A camphorata has the ability to cause apoptosis in various cancer cells. Conversely, underlying molecular mechanisms and any beneficial effects remain unknown. This study shows anticancer efficacy for both T sinensis and A camphorata co-treatments that target HL-60 cells. The combination index values indicate that 40 µg/mL of T sinensis and 25 µg/mL of A camphorata as a combined treatment shows a synergetic effect, which reduces HL-60 cell proliferation. Alternately, this treatment exhibited no cytotoxic effects for human umbilical vein endothelial cells. Western blot data showed that T sinensis and A camphorata as a combined treatment result in augmented expression of apoptosis, cytochrome c release, Bcl-2 inhibition, expression of Bax, Fas, and FasL, as well as the cleavage of Bid in HL-60 cells. Moreover, this combined treatment overshadowed monotherapy in its ability to inhibit uPAR, MMP-9, MMP-2, COX-2 expression, and PGE2 secretions. Our study strongly implies that this combined treatment offers more beneficial effects to suppress and treat leukemia due to apoptosis-mediated cell inhibition. Further in vivo studies related to the combined treatment could establish its future potential.

Toona sinensis modulates autophagy and cytokines in lipopolysaccharide-induced RAW 264.7 macrophages.

Toona sinensis (TS) is a medicinal herb possessing anti-apoptotic, anti-oxidant, and anti-inflammatory properties and is used to treat diabetes, cancer, and inflammatory diseases. In traditional Chinese medicine theory, TS clears dampness and heat, strengthens the stomach function, and regulates vital energy flow. TS is also used as an astringent and a pesticide. In this study, we aimed to evaluate how TS influences autophagy and cytokines during the inflammatory process in RAW 264.7 macrophages. The treatment groups were pre-supplemented with TS leaf extract; rapamycin was used to enhance autophagy and lipopolysaccharide (LPS) was used to induce inflammation. The expression of autophagy-related proteins was analyzed by western blotting. The survival rate of, and chemokine expression and oxidative stress in the cells were also assessed. TS leaf extract inhibited mammalian target of rapamycin (mTOR) phosphorylation at site S2448 in the macrophages. At relatively higher concentrations (50 and 75 µg/mL), TS elevated the expression of light chain 3 II (LC3-II), which further modulated autophagy. Pre-supplementation with TS leaf extract elevated the total glutathione (GSH) level and GSH/oxidized GSH (GSSG) ratio, but it decreased the GSSG, total nitric oxide, nitrate, nitrite, malondialdehyde, and superoxide anion levels. TS reversed the effects of LPS-induced cytokines, including interleukin (IL)-6 and IL-10. TS did not induce significant toxicity at the studied concentrations. In conclusion, TS leaf extract may modulate autophagy during inflammation. Furthermore, it may prevent cell damage via anti-inflammation and anti-oxidation. Thus, this study supports the ethnomedical use of TS in the prevention of inflammation-related diseases.

Polyphenols from Toona sinensiss Seeds Alleviate Neuroinflammation Induced by 6-Hydroxydopamine Through Suppressing p38 MAPK Signaling Pathway in a Rat Model of Parkinson's Disease.

Polyphenols from Toona sinensis seeds (PTSS) have demonstrated anti-inflammatory effects in various diseases, while the anti-neuroinflammatory effects still remain to be investigated. We aimed to investigate the effects of PTSS on Parkinson's disease and underlying mechanisms using a rat model. We employed 6-hydroxydopamine (6-OHDA) to male Sprague Dawley (SD) rats and PC12 cells to construct the in vivo and vitro models of PD and dopaminergic (DA) neuron injury, respectively. Cell viability was detected by cell counting kit-8 (CCK-8) assay and protein levels of inflammatory mediators and some p38 MAPK pathway molecules were investigated by immunohistochemistry and Western blot analyses. The results showed that 6-OHDA significantly increased protein levels of inflammatory mediators, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor α (TNF-α), which could be reversed by PTSS through suppressing the p38 MAPK pathway. The anti-inflammatory effects of PTSS were significantly enhanced by the specific p38 inhibitor of SB203580 in vitro. The present work suggests that PTSS can exert anti-inflammatory effects on PD models, which may be attributed to the suppression of p38 MAPK signaling pathway.

Toonasindiynes A-F, new polyacetylenes from Toona sinensis with cytotoxic and anti-inflammatory activities.

The plants of genus Toona are well known for diverse limonoid secondary metabolites, while polyacetylenes are rarely found from Toona species. In this work, six new polyacetylenes toonasindiynes A-F (1-6) and six known analogues (7-12) were isolated from the root bark of Toona sinensis. Their structures and absolute configurations were elucidated by HRESIMS, 1D and 2D NMR spectroscopic analysis, modified Mosher's method, and biosynthetic consideration. These polyacetylenes share the same 4,6-diyne moiety with different side chain length and different oxidation degree. Bioactivity screening revealed the cytotoxic activity of 3, 5, 9, and 11 against U2OS cells, and the inhibitory effects on nitric oxide (NO) production of 1, 2, 5, 8, 9, and 11 in lipopolysaccharide-induced RAW 264.7 cells.