A Biomimetic Multifunctional Nanoframework for Symptom Relief and Restorative Treatment of Acute Liver Failure.

Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.

Mechanical properties of trabeculae and osteocyte morphology change significantly in different areas of the necrotic femoral head.

Background: Osteonecrosis of the femoral head is a complex hip ailment. The precise changes in bone tissue during the disease's onset remain unclear. It is vital to assess both the quantity and quality of the trabecular state in a necrotic femoral head. Aim: This study aims to identify and compare the ultrastructural changes in osteocyte morphology and nanomechanical characteristics within various regions of necrotic femoral heads. Methods: Between December 2016 and May 2023, we gathered ten necrotic femoral heads from patients and five femoral heads from cadavers. The samples from the necrotic femoral heads were categorized into three areas: necrotic, sclerotic, and normal. Our assessment methods encompassed hematoxylin and eosin staining, sclerostin (SOST) immunohistochemistry, micro-computed tomography, nanoindentation, and acid-etched scanning electron microscopy. These techniques enabled us to examine the SOST expression, trabecular microstructure, micromechanical properties of trabeculae, and modifications in osteocyte morphology at the ultrastructural level. Results: The protein level of SOST was found to be lower in the sclerotic area. In the necrotic area, decreased values of bone volume fraction, trabecular thickness, and trabecular number and an increased value of trabecular separation were found. Conversely, in the sclerotic area, higher mean values of bone volume fraction, trabecular number, and trabecular thickness and lower trabecular separation indicated significant changes in the structural characteristics of trabeculae. Compared with the healthy area, the elastic modulus and hardness in the sclerotic area were significantly higher than those in the necrotic, normal, and control areas, while those in necrotic areas were significantly lower than those in the healthy area. The number of osteocytes tended to increase in the sclerotic area with more canalicular cells compared to the healthy area and control group. Conclusion: These results imply that the stress distribution within the sclerotic area could potentially lead to enhanced trabecular quality and quantity. This effect is also reflected in the increased count of osteocytes and their canaliculars. It is plausible that the sclerotic trabecular bone plays a pivotal role in the repair of necrotic femoral heads.

Limonoids from the roots of Melia azedarach and their anti-inflammatory activity.

Twelve undescribed limonoids, meliazedarines J-U (1-12), along with a known one, were isolated from the roots of Melia azedarach. Their structures were elucidated by extensive spectroscopic investigations, X-ray diffraction analyses, and ECD calculations. Compounds 1-8 were identified as ring intact limonoids, while compounds 9-12 were established as ring C-seco ones. The anti-inflammatory potential of compounds 1-4, 6, 8, 9, and 11-13 was evaluated on macrophages. Compounds 1, 3, 4, 6, and 9 significantly suppressed nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, among them compound 3 showed the best inhibitory effect with an IC50 value of 7.07 ± 0.48 µΜ. Furthermore, compound 3 effectively reduced interleukin-1ß secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. The results strongly suggested that limonoids from the roots of M. azedarach might be candidates for treating inflammation-related diseases.

Total saponins from Panax japonicus attenuate acute alcoholic liver oxidative stress and hepatosteatosis by p62-related Nrf2 pathway and AMPK-ACC/PPARα axis in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax japonicus (T. Nees) C.A. Mey. (PJ) has been used as a tonic traditional Chinese medicine (TCM) for years. Based on its meridian tropism in liver, spleen, and lung, PJ was popularly used to enhance the function of these organs. It is originally recorded with detoxicant effect on binge drink in Ben Cao Gang Mu Shi Yi, a persuasive Chinese materia medica. And binge dink has a close relationship with alcoholic liver disease (ALD). Hence, it's meaningful to investigate whether PJ exerts liver protection against binge drink toxicity. AIM OF THE STUDY: This investigation was carried out not only to emphasize the right recognition of total saponins from PJ (SPJ), but also to study on its sober-up effectiveness and defensive mechanism against acute alcoholic liver injury in vivo and in vitro. MATERIALS AND METHODS: SPJ constituents were verified by HPLC-UV analysis. In vivo, acute alcoholic liver oxidative stress and hepatosteatosis were established by continuous ethanol gavage to C57BL/6 mice for 3 days. SPJ was pre-administered for 7 days to investigate its protective efficacy. Loss of righting reflex (LORR) assay was employed to assess anti-inebriation effect of SPJ. Transaminases levels and hematoxylin and eosin (H&E) staining were measured to indicate the alcoholic liver injury. Antioxidant enzymes were measured to evaluate the oxidative stress degree in liver. Measurement of hepatic lipid accumulation was based on Oil Red O staining. Levels of inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). In vitro, HepG2 cells were treated with ethanol for 24 h, and SPJ was pre-administered for 2 h. 2,7-dichlorofluorescein diacetate (DCFH-DA) was used as a probe to indicate reactive oxygen species (ROS) generation. Nrf2 activation was verified by the favor of specific inhibitor, ML385. The nuclear translocation of Nrf2 was indicated with immunofluorescence analysis. Proteins expressions of related pathways were determined by Western blotting. RESULTS: Oleanane-type saponins are the most abundant constituents of SPJ. In this acute model, SPJ released inebriation of mice in a dose dependent manner. It decreased levels of serum ALT and AST, and hepatic TG. Besides, SPJ inhibited CYP2E1 expression and reduced MDA level in liver, with upregulations of antioxidant enzymes GSH, SOD and CAT. p62-related Nrf2 pathway was activated by SPJ with downstream upregulations of GCLC and NQO1 in liver. AMPK-ACC/PPARα axis was upregulated by SPJ to alleviate hepatic lipidosis. Hepatic IL-6 and TNF-α levels were downregulated by SPJ, which indicated a regressive lipid peroxidation in liver. In HepG2 cells, SPJ reduced ethanol-exposed ROS generation. Activated p62-related Nrf2 pathway was verified to contribute to the alleviation of alcohol-induced oxidative stress in hepatic cells. CONCLUSION: This attenuation of hepatic oxidative stress and steatosis suggested the therapeutic value of SPJ for ALD.

Microalgae Microneedle Supplies Oxygen for Antiphotoaging Treatment.

UV exposure often triggers photoaging of the skin. Pharmacological treatment suffers from severe side effects as well as poor efficacy because of insufficient skin penetration. Dissolved oxygen has been previously shown to reverse photoaged skin; however, the treatment is often limited by the availability of equipment (e.g., high-pressure oxygen). Poor oxygen diffusion into the skin has also limited its therapeutic efficacy. Herein, we developed a microneedle patch to deliver living microalgae to the deeper layers of the skin for efficient oxygenation and reversal of photoaging. The continuous release of oxygen from microalgae in the skin through photosynthesis reversed the inflammatory microenvironment and reduced reactive oxygen species levels in the photodamaged skin, leading to collagen regeneration and reduced wrinkles. This study provides not only a means for highly efficient skin oxygenation and reversal of photoaging but also an important theoretical basis for the clinical treatment of photoaging.

Rational Design of Covalent Kinase Inhibitors by an Integrated Computational Workflow (Kin-Cov).

Covalent kinase inhibitors (CKIs) hold great promise for drug development. However, examples of computationally guided design of CKIs are still scarce. Here, we present an integrated computational workflow (Kin-Cov) for rational design of CKIs. The design of the first covalent leucine-zipper and sterile-α motif kinase (ZAK) inhibitor was presented as an example to showcase the power of computational workflow for CKI design. The two representative compounds, 7 and 8, inhibited ZAK kinase with half-maximal inhibitory concentration (IC50) values of 9.1 and 11.5 nM, respectively. Compound 8 displayed an excellent ZAK target specificity in Kinome profiling against 378 wild-type kinases. Structural biology and cell-based Western blot washout assays validated the irreversible binding characteristics of the compounds. Our study presents a rational approach for the design of CKIs based on the reactivity and accessibility of nucleophilic amino acid residues in a kinase. The workflow is generalizable and can be applied to facilitate CKI-based drug design.

Germacrane-type sesquiterpenoids from the flowers of Chrysanthemum indicum with hepatoprotective activity.

Two new germacrane-type sesquiterpenoids, chrysanthemolides A (1) and B (2), and four known germacrane-type sesquiterpenoids, hanphyllin (3), 3ß-hydroxy-11α,13-dihydro-costunolide (4), costunolide (5), and 6,7-dimethylmethylene-4-aldehyde-1ß-hydroxy-10(15)-ene-(4Z)-dicyclodecylene (6), were isolated and identified from the flowers of Chrysanthemum indicum. The structures of the new compounds were elucidated via high resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D and 2D nuclear magnetic resonance (NMR) spectra and electronic circular dichroism (ECD). Meanwhile, all the isolates were tested for their hepatoprotective activity in tert-butyl hydroperoxide (t-BHP) injured AML12 cells. Compounds 1, 2, and 4 showed significant protective effects at 40 µM, comparable with the positive control resveratrol at 10 µM. As the most potent one, compound 1 was chosen for further studies. Compound 1 dose-dependently increased the viability of t-BHP-injured AML12 cells. Furthermore, compound 1 decreased reactive oxygen species accumulation, while increased glutathione level, heme oxygenase-1 level and superoxide dismutase activity, through anchoring in the binding site of Kelch domain of the Kelch-like ECH-associated protein 1 (Keap1) to promote the dissociation of nuclear factor erythroid 2-related factor 2 from Keap1 and translocation to nuclei. In summary, germacrane-type sesquiterpenoids from C. indicum might be further developed to protect liver against oxidative damage.

Combining frog-leg lateral view may serve as a more sensitive X-ray position in monitoring collapse in osteonecrosis of the femoral head.

Load-bearing capacity of the bone structures of anterolateral weight-bearing area plays an important role in the progressive collapse in osteonecrosis of the femoral head (ONFH). The purpose of this study is to assess the efficacy of combined evaluation of anteroposterior (AP) and frog-leg lateral (FLL) view in diagnosing collapse. Between December 2016 and August 2018, a total of 478 hips from 372 patients with ONFH (268 male, 104 female; mean age 37.9 ± 11.4 years) were retrospectively evaluated. All patients received standard AP and FLL views of hip joints. Japanese Investigation Committee (JIC) classification system was used to classify necrotic lesion in AP view. Anterior necrotic lesion was evaluated by FLL view. All patients with pre-collapse ONFH underwent non-operative hip-preserving therapy. The collapse rates were calculated and compared with Kaplan-Meier survival analysis with radiological collapse as endpoints. Forty-four (44/478, 9.2%) hips were classified as type A, 65 (65/478, 13.6%) as type B, 232 (232/478, 48.5%) as type C1 and 137 (137/478, 28.7%) as type C2. Three hundred cases (300/478, 62.5%) were collapsed at the initial time point. Two hundred and twenty six (226/300, 75.3%) hips and 298 (298/300, 99.3%) hips collapse were identified with AP view and FLL view, respectively. An average follow-up of 37.0 ± 32.0 months was conducted to evaluate the occurrence of collapse in 178 pre-collapse hips. Collapses occurred in 89 hips (50.0%). Seventy-seven (77/89, 86.5%) hips were determined with AP view alone and 85 (85/89, 95.5%) hips were determined with the combination of AP and FLL views. The collapse rates at five years were reported as 0% and 0%, 16.2% and 24.3%, 58.3% and 68.1% and 100% and 100% according to AP view alone or combination of AP and FLL views for types A, B, C1 and C2, respectively. The collapse can be diagnosed more accurately by combination of AP and FLL views. Besides, JIC type A and type B ONFH can be treated with conservative hip preservation, but pre-collapse type C2 ONFH should be treated with joint-preserving surgery. Type C1 needs further study to determine which subtype has potential risk of collapse.

Triterpenoids from the fruits of Melia azedarach L. and their cytotoxic activities.

Eleven undescribed tetracyclic triterpenoids, meliazedarachins A-K, along with twenty-six known compounds were isolated from the fruits of Melia azedarach L.. Their structures were determined by HRESIMS, UV, IR, NMR, X-ray diffraction, electronic circular dichroism (ECD) spectra, and the modified Mosher's method. The cytotoxic activities of all the isolates were measured. Meliazedarachin K and mesendanin N showed cytotoxicity against five human cancer cell lines with IC50 values ranging from 9.02 to 31.31 µM. Meliazedarachin K showed significant cytotoxicity against HCT116 cell line with IC50 value of 9.02 ± 0.84 µM. 21α-methylmelianodiol showed significant cytotoxicity against HCT116 and RKO cell lines with IC50 values of 10.16 ± 1.22 and 8.57 ± 0.80 µM, respectively.

Corrigendum: The Therapeutic Effect of Huo Xue Tong Luo Capsules in Association Research Circulation Osseous (ARCO) Stage II Osteonecrosis of the Femoral Head: A Clinical Study With an Average Follow-up Period of 7.95 Years.

[This corrects the article DOI: 10.3389/fphar.2021.773758.].

Biflavonoids from the twigs and leaves of Cephalotaxus oliveri Mast. and their α-glucosidase inhibitory activity.

Three new biflavonoids, umcephabiovins C - E (1 - 3), along with fourteen known compounds were isolated from the twigs and leaves of Cephalotaxus oliveri. Their structures and configurations were elucidated by UV, IR, NMR, ECD, and HR-ESI-MS spectra. Compounds 1 - 3 exhibited significant α-glucosidase inhibitory activity with IC50 values of 7.05 ± 2.66, 24.45 ± 4.73, and 1.84 ± 1.14 µM, respectively. Compound 11 showed moderate cytotoxicity against the BaF3/T315I cell line.

The Therapeutic Effect of Huo Xue Tong Luo Capsules in Association Research Circulation Osseous (ARCO) Stage II Osteonecrosis of the Femoral Head: A Clinical Study With an Average Follow-up Period of 7.95 Years.

Background: Huo Xue Tong Luo (HXTL) capsules are an oral preparation that could relieve pain and ameliorate osteonecrosis in patients with asymptomatic osteonecrosis of femoral head (ONFH). We wanted to verify whether it could be a treatment option for ARCO stage II ONFH. Methods: A total of 44 patients (66 hips) with ARCO stage II ONFH were recruited from June 1996 to October 2013 (clinical trial registry number: ChiCTR-RPC-15006,290). HXTL capsules were given under a specific protocol, and the endpoint was set as femoral head collapse. The clinical indicators [including visual analog scale (VAS) and Harris Hip Score (HHS)] and radiological indicators [including Tonnis classification, ARCO stage, Japanese Investigation Committee (JIC) classification, lateral preserved angle (LPA), anterior preserved angle (APA), and combined preserved angle (CPA)] before and after treatment were compared. Kaplan-Meier survival analysis and Cox regression analysis were used to identify the risk factors associated with femoral head collapse. Result: Twenty-six males and 18 females with an average age of 38.3 ± 2.8 were followed for an average of 7.95 years. Forty-six of the 66 (69.7%) hips had no progression in pain or collapse, and patients exhibited a higher HHS (p < 0.05) after therapy. Twenty of the 66 (30.3%) hips progressed in Tonnis classification and ARCO stage, but only one of the 66 (1.5%) hips required total hip arthroplasty (THA). The Kaplan-Meier survivorship curve suggested that the survival rates were 96.97% at 5 years, 69.15% at 10 years, and 40.33% at 15 years. Patients with type A necrotic lesions on anteroposterior (AP) and frog-leg lateral (FLL) radiographs revealed 100% survival rates. Multivariate Cox regression analysis revealed that patients with an LPA ≤ 60.9 exhibited a 3.87 times higher risk of collapse of the femoral head [95% confidence interval (CI), 1.241-5.673] than did those patients with an LPA>60.9. Conclusion: HXTL capsules could be a treatment option for ARCO stage II ONFH, resulting in improved hip function and delayed progression to femoral head collapse, especially when the anterior and lateral portions of the femoral head were not affected. However, an LPA of less than 60.9° may be a risk factor for collapse of the femoral head. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx?projZ10829].

Discovery of Three New Monoterpenoid Indole Alkaloids from the Leaves of Gardneria multiflora and Their Vasorelaxant and AChE Inhibitory Activities.

Three novel monoterpenoid indole alkaloids gardflorine A (1), gardflorine B (2), and gardflorine C (3) were isolated from the leaves of Gardneria multiflora. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and circular dichroism experiments. All the compounds were evaluated for their vasorelaxant and acetylcholinesterase (AChE) inhibitory activities. Compound 1 exhibited potent vasorelaxant activity, with an EC50 value of 8.7 µM, and compounds 2 and 3 showed moderate acetylcholinesterase (AChE) inhibitory activities, with IC50 values of 26.8 and 29.2 µM, respectively.

Honokiol: A naturally occurring lignan with pleiotropic bioactivities.

Honokiol is the dominant biphenolic compound isolated from the Magnolia tree, and has long been considered as the active constituent of the traditional Chinese herb, 'Houpo', which is widely used to treat symptoms due to 'stagnation of qi'. Pharmacological studies have shown that honokiol possesses a wide range of bioactivities without obvious toxicity. Honokiol protects the liver, kidneys, nervous system, and cardiovascular system through reducing oxidative stress and relieving inflammation. Moreover, honokiol shows anti-diabetic property through enhancing insulin sensitivity, and anti-obese property through promoting browning of adipocytes. In vivo and in vitro studies indicated that honokiol functions as an anti-cancer agent through multiple mechanisms: inhibiting angiogenesis, promoting cell apoptosis, and regulating cell cycle. A variety of therapeutic effects of honokiol may be associated with its physiochemical properties, which make honokiol readily cross the blood brain barrier and the blood-cerebrospinal fluid barrier, with high bioavailability. In the future, more clinical researches on honokiol are needed to fully authenticate its therapeutic values.

Cucurbit[8]uril-based supramolecular hydrogels for biomedical applications.

As a member of the cucurbit[n]uril family (where n denotes the number of glycoluril units), cucurbit[8]uril (CB[8]) possesses a large cavity volume and is able to accommodate two guests simultaneously. Therefore, CB[8] has been adapted as a dynamic noncovalent crosslinker to form various supramolecular hydrogels. These CB[8]-based hydrogels have been investigated for various biomedical applications due to their good biocompatibility and dynamic properties afforded by host-guest interactions. In this review, we summarize the hydrogels that have been dynamically fabricated via supramolecular crosslinking of polymers by CB[8] reported during the past decade, and discuss their design principles, innovative applications in biomedical science and their future prospects.

Synthesis of an AIEgen functionalized cucurbit[7]uril for subcellular bioimaging and synergistic photodynamic therapy and supramolecular chemotherapy.

Aggregation-induced emission (AIE) based fluorophores (AIEgens) have attracted increasing attention for biomedical applications due to their unique optical properties. Here we report an AIE photosensitizer functionalized CB[7], namely AIECB[7], which could spontaneously self-assemble into nanoaggregates in aqueous solutions. Interestingly, the carbonyl-lace of CB[7] may potentially act as a proton acceptor in an acidic environment to fine-tune the fluorescence and singlet oxygen generation of AIECB[7] nanoaggregates by regulating the inner stacking of AIEgens. Additionally, benefiting from the guest-binding properties of CB[7], oxaliplatin was included into AIECB[7] nanoaggregates for combined photodynamic therapy and supramolecular chemotherapy. To show the modular versatility of this supramolecular system, a hypoxia-activatable prodrug banoxantrone (AQ4N) was loaded into AIECB[7] nanoaggregates, which exhibited synergistic antitumor effects on a multicellular tumor spheroid model (MCTS). This work not only provides AIECB[7] for versatile theranostic applications, but also offers important new insights into the design and development of macrocycle-conjugated AIE materials for diverse biomedical applications.

Reciprocal Regulation between Fur and Two RyhB Homologs in Yersinia pestis, and Roles of RyhBs in Biofilm Formation.

OBJECTIVE: To investigate reciprocal regulation between Fur and two RyhB homologs in Yersinia pestis( Y. pestis), as well as the roles of RyhBs in biofilm formation. METHODS: Regulatory relationships were assessed by a combination of colony morphology assay, primer extension, electrophoretic mobility shift assay and DNase I footprinting. RESULTS: Fur bound to the promoter-proximal DNA regions of ryhB1 and ryhB2 to repress their transcription, while both RyhB1 and RyhB2 repressed the expression of Fur at the post-transcriptional level. In addition, both RyhB1 and RyhB2 positively regulated Y. pestis biofilm exopolysaccharide (EPS) production and the expression of hmsHFRS and hmsT. CONCLUSION: Fur and the two RyhB homologs exert negative reciprocal regulation, and RyhB homologs have a positive regulatory effect on biofilm formation in Y. pestis.

[Effects of Biochar and Straw on Soil N2O Emission from a Wheat Maize Rotation System].

The effects of biochar and straw return on soil N2O emissions were studied in the winter wheat-summer maize rotation system of intensively farmed land in North China to provide a theoretical basis for N2O emission reduction and the efficient straw utilization. The experiment included the following four treatments:① Control (CK); ② Biochar application at a rate of 9.0 t·(hm2·a)-1 (C); ③ Straw return (SR); and ④ Straw return plus biochar application at a rate of 9.0 t·(hm2·a)-1 (C+SR). The results showed that in the wheat season, the CK treatment showed a slight decrease in soil N2O emission while the SR and C+SR treatments promoted soil N2O emission by 47.4% and 71.8%, respectively. In the maize-growing season, the CK treatment reduced soil N2O emission by 29.8% while the SR and C+SR treatments increased soil N2O emission by 13.4% and 35.8%, respectively. During the wheat-growing season, the soil water, NH4+-N, and MBN content were the main environmental factors affecting N2O emissions; during the maize-growing season, NO3--N, NH4+-N, and MBC content were the main environmental factors affecting emissions. Based on our results, the application of biochar to cropland is an effective option for mitigating greenhouse gas emissions, whereas direct straw return to fields might not be an effective strategy. More research is now needed to examine the effect of the return of straw of different maturity on N2O emissions.

Supramolecular nanomedicine for selective cancer therapy via sequential responsiveness to reactive oxygen species and glutathione.

Cancer cells are generally immersed in an oxidative stress environment with a high intracellular reduction level. Thus, nanocarriers with sequential responsiveness to oxidative and reductive species, matching the traits of high oxidation in the tumor tissue microenvironment and high reduction potential inside cancer cells, are highly desired for specific cancer therapy. Herein, we report a supramolecular nanomedicine comprised of a reduction-responsive nanoparticle (NP) core whose surface was modified by an oxidation-responsive polyethylene glycol (PEG) derivative via strong host-guest interactions. In this delicate design, the PEGylation of NPs not only reduced their immunogenicity and extended systemic circulation, but also enabled oxidation-responsive de-PEGylation in the tumor tissues and subsequent intracellular payload release in response to glutathione (GSH) inside tumor cells. As a proof of concept, this supramolecular nanomedicine exhibited specific chemotherapeutic effects against cancer in vitro and in vivo with a decent safety profile.

Bioactive Limonoids and Triterpenoids from the Fruits of Melia azedarach.

Nine new limonoids, meliazedarines A-I (1-9), seven known analogues (10-16), and five known triterpenoids (17-21) were isolated from the fruits of Melia azedarach. Their structures were determined by analysis of 1D and 2D NMR, HRESIMS, X-ray diffraction, and electronic circular dichroism (ECD) data. Compound 7 showed significant cytotoxicity against the HCT116 cell line with IC50 values of 0.3 ± 0.1 µM.