Boswellianols A-I, Structurally Diverse Diterpenoids from the Oleo-Gum Resin of Boswellia carterii and Their TGF-ß Inhibition Activity.

Olibanum, a golden oleo-gum resin from species in the Boswellia genus (Burseraceae family), is a famous traditional herbal medicine widely used around the world. Previous phytochemical studies mainly focused on the non-polar fractions of olibanum. In this study, nine novel diterpenoids, boswellianols A-I (1-9), and three known compounds were isolated from the polar methanolic fraction of the oleo-gum resin of Boswellia carterii. Their structures were determined through comprehensive spectroscopic analysis as well as experimental and calculated electronic circular dichroism (ECD) data comparison. Compound 1 is a novel diterpenoid possessing an undescribed prenylmaaliane-type skeleton with a 6/6/3 tricyclic system. Compounds 2-4 were unusual prenylaromadendrane-type diterpenoids, and compounds 5-9 were new highly oxidized cembrane-type diterpenoids. Compounds 1 and 5 showed significant transforming growth factor ß (TGF-ß) inhibitory activity via inhibiting the TGF-ß-induced phosphorylation of Smad3 and the expression of fibronectin and N-cadherin (the biomarker of the epithelial-mesenchymal transition) in a dose-dependent manner in LX-2 human hepatic stellate cells, indicating that compounds 1 and 5 should be potential anti-fibrosis agents. These findings give a new insight into the chemical constituents of the polar fraction of olibanum and their inhibitory activities on the TGF-ß/Smad signaling pathway.

Comparison of hysterectomy cases performed by transvaginal natural orifice transluminal endoscopic surgery: A paired sample cross-sectional study.

This study aimed to investigate the feasibility, indications, and benefits of transvaginal natural orifice transluminal endoscopic surgery (v-NOTES) hysterectomy for nonmalignant gynecological diseases. The clinical data, including the baseline information and surgical conditions of 81 patients who underwent v-NOTES hysterectomy for nonmalignant gynecological diseases in a tertiary university hospital from October 2018 to August 2022, were retrospectively analyzed and compared with the total laparoscopic hysterectomy group (200 cases) and the transumbilical laparoendoscopic Single Site Surgery group (150 cases). In comparison with the other 2 groups, the highest proportion of patients in the v-NOTES group had cervical intraepithelial neoplasia. Accordingly, mean preoperative uterine volume measured by sonography was significantly smaller in the v-notes group. In the v-NOTES group, the mean number of vaginal deliveries and age were significantly higher, while the mean number of previous abdominal surgeries was lower compared to the other 2 groups. The V-NOTES group had a shorter operation time, shorter postoperative urinary catheter insertion time, earlier intestinal recovery days, shorter hospital stay, and lower visual analogue scale scores after surgery, and the differences were statistically significant. When indicated appropriately, v-NOTES hysterectomy can be a feasible and advantageous surgical modality. In particular, in comparison to the laparoendoscopic Single Site Surgery and total laparoscopic hysterectomy groups, the v-NOTES group had advantages in postoperative recovery and had more aesthetic surgical results.

Functionalized Fe-Doped Carbon Dots Exhibiting Dual Glutathione Consumption to Amplify Ferroptosis for Enhanced Cancer Therapy.

Nonapoptotic ferroptosis is a promising cancer treatment which offers a solution to the multidrug resistance of conventional apoptosis-induced programmed cancer cell death therapies. Reducing intracellular glutathione (GSH) is essential for inducing excess ROS and has been considered a crucial process to trigger ferroptosis. However, treatments reducing GSH alone have not produced satisfactory effects due to their restricted target. In this regard, FeCDs (Fe3+-modified l-histidine -sourced carbon dots) with dual GSH-consumption capabilities were constructed to engineer ferroptosis by self-amplifying intratumoral oxidative stress. Carbon dots have the ability to consume GSH, and the introduction of Fe3+ can amplify the GSH-consuming ability of CDs, reacting with excess H2O2 in the tumor microenvironment to generate highly oxidized •OH. This is a novel strategy through synergistic self-amplification therapy combining Fe3+ and CDs with GSH-consuming activity. The acid-triggered degradation material (FeCDs@PAE-PEG) was prepared by encapsulating FeCDs in an oil-in-water manner. Compared with other ferroptosis-triggering nanoparticles, the established FeCDs@PAE-PEG is targeted and significantly enhances the consumption efficiency of GSH and accumulation of excess iron without the involvement of infrared light and ultrasound. This synergistic strategy exhibits excellent ferroptosis-inducing ability and antitumor efficacy both in vitro and in vivo and offers great potential for clinical translation of ferroptosis.

Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury.

Introdcution: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary. Methods: We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells. Results: Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells. Discussion: Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.

TfOH-Catalyzed Cascade C-H/N-H Chemo-/Regioselective Annulation of Indole-2-carboxamides with Benzoquinones for the Construction of Anticancer Tetracyclic Indolo[2,3-c]quinolinones.

An efficient TfOH-catalyzed cascade C-H/N-H annulation of indole-2-carboxamides with benzoquinones has been developed for the synthesis of tetracyclic indolo[2,3-c]quinolinones. This reaction exhibits excellent chemo-/regioselectivity, achieving functionalization of the C-3 of indole and N-H of the amide moiety to form the new C-C and C-N bonds. Various expected products were synthesized from readily available starting materials in good to high yields with a wide substrate scope and good functional group tolerance. Among all synthetic products, 3d showed the most potent cytotoxicity toward the 4T1 cancer cell line with an IC50 value of 0.62 ± 0.05 µM. In vivo study demonstrated that 3d remarkably suppressed 4T1 xenograft tumor growth without body weight loss.

Cryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis.

As a characteristic transcription factor in solid tumors, hypoxia inducible factor-1 (HIF-1) acts as a master regulator in breast cancer progression. Cryptolepine, as a natural alkaloid, noticeably inhibited HIF-1 transcriptional activity and decreased the protein expression of hypoxia-induced HIF-1α in breast cancer cells. Further study showed that cryptolepine blocked HIF-1-mediated glycolysis and suppressed the expression of multiple glycolysis enzymes, resulting in a decrease in ATP production in hypoxic T47D and 4T1 cells. Meanwhile, cryptolepine displayed potent suppressive effect on tumor growth in a dose-dependent manner. In 4T1 tumor xenografts, cryptolepine reduced HIF-1α protein expression, and thus decreased the levels of both lactate acid and ATP productions. The mechanistic study revealed that cryptolepine could effectively suppress the process of HIF-1α mRNA translation rather than transcription, which was attributed to the inhibition on the phosphorylation of eIF4E regulated by both MAPK and mTOR signaling pathways. Collectively, current findings suggested that cryptolepine possesses the potential to treat breast cancers by modulating HIF-1 both in vitro and in vivo.

Pharmacological targeting transient receptor potential canonical channel 6 modulates biological behaviors for cervical cancer HeLa and SiHA cell.

BACKGROUND: This study aimed to observe the effect of transient receptor potential canonical channel 6 (TRPC6) antagonist 1-(ß-[3-(4-method-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrate (SKF-96365) and its agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) on the proliferation of cervical cancer cell lines HeLa and SiHa, deoxyribonucleic acid (DNA) synthesis, cell migration, and TRPC6 expression. METHOD: Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of TRPC6 in HeLa and SiHa cells. The tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the 5-ethynyl -2'- deoxyuridine (EdU) fluorescence detection assay, and a scratch test were used to detect the changes of proliferation, DNA synthesis and cell migration of HeLa and SiHa cells after SKF 96,365 and OAG acted on HeLa and SiHa cells for different lengths of time. RT-qPCR was used to detect expression changes of TRPC6 SKF-96365 and OAG treated HeLa and SiHa cells. RESULTS: TRPC6 was expressed both in HeLa and SiHa cells. The MTT assay showed that after 24 h of SKF-96365 treatment, compared with the control group, the proliferation of HeLa and SiHa cells was inhibited, and there was a statistically significant difference (p < 0.05). After 24 h of OAG, compared with the control group, the proliferation of HeLa and SiHa cells had increased, and there was a statistically significant difference (p < 0.05). EdU fluorescence detection showed that SKF-96365 could inhibit the DNA synthesis of HeLa and SiHa cells, and OAG could promote the DNA synthesis of HeLa and SiHa cells (p < 0.05) in HeLa and SiHa cell lines. CONCLUSION: The high expression of calcium channel TRPC6 in HeLa and SiHa tissues may be related to the malignant behavior of cervical cancer cell lines HeLa and SiHa. This calcium channel may be a new target for the prevention and treatment of cervical cancer.

I2-Catalyzed Carbonylation of α-Methylene Ketones to Synthesize 1,2-Diaryl Diketones and Antiviral Quinoxalines in One Pot.

An efficient approach for the synthesis of 1,2-diaryl diketones was developed from readily available α-methylene ketones by catalysis of I2. In the same oxidation system, a novel one-pot procedure was established for the construction of antiviral and anticancer quinoxalines. The reactions proceeded well with a wide variety of substrates and good functional group tolerance, affording desired compounds in moderate to excellent yields. Quinoxalines 4ca and 4ad inhibited viral entry of SARS-CoV-2 spike pseudoviruses into HEK-293T-ACE2h host cells as dual blockers of both human ACE2 receptor and viral spike RBD with IC50 values of 19.70 and 21.28 µM, respectively. In addition, cytotoxic evaluation revealed that 4aa, 4ba, 4ia, and 4ab suppressed four cancer cells with IC50 values ranging from 6.25 to 28.55 µM.

Ultrasound-guided single thoracic paravertebral nerve block and erector spinae plane block for perioperative analgesia in thoracoscopic pulmonary lobectomy: a randomized controlled trial.

OBJECTIVE: To explore the effect of a single preoperative ultrasound-guided thoracic paravertebral nerve block (TPVB) and erector spinae plane block (ESPB) for perioperative analgesia in thoracoscopic pulmonary lobectomy. METHODS: Seventy-two patients aged 40-70 years who underwent thoracoscopic pulmonary lobectomy under general anesthesia were enrolled and randomly divided into the control group (Group C), the TPVB group (Group T) and the ESPB group (Group E). The primary observation indicators included the visual analogue scale (VAS) at 1, 6, 12, 24, and 48 h postoperatively at rest and with a cough. The secondary observation indicators included the intraoperative sufentanil consumption, anesthesia awakening time and extubation time, the sufentanil consumption in the analgesic pump, and flurbiprofen ester consumption for remedial analgesia within 48 h after surgery and the incidence of postoperative adverse events. RESULTS: The intraoperative sufentanil consumption, anesthesia awakening time, and extubation time were lower in groups T and E than those in group C (p < 0.05). Patients in group T had lower VAS scores at rest and with a cough at 1, 6, and 12 h postoperatively than in group C at the same time points (p < 0.05). The VAS scores at rest at 1 and 6 h postoperatively and coughing status at 1, 6, and 12 h postoperatively were lower in group E than in group C at the same time points (p < 0.05). CONCLUSION: The ultrasound-guided preoperative single TPVB and ESPB for thoracoscopic pulmonary lobectomy could both reduce the postoperative pain VAS score and reduce the dose of perioperative sufentanil and postoperative remedial analgesics.

Linc00467 promotion of gastric cancer development by directly regulating miR-7-5p expression and downstream epidermal growth factor receptor.

Linc00467 is a vital regulator in tumor progression. This study explores the molecular mechanisms of linc00467 in gastric cancer (GC). Linc00467 expression was obtained and analyzed in GC tissue through exploration in the cancer genome atlas database. Then, real-time quantitative polymerase chain reaction was used to detect linc000467 expression in GC cells. Cell functions were observed using cell counting Kit-8, Transwell assay, Western blotting to testify the proliferation, migration, invasion, and the relative expression of epidermal growth factor receptor (EGFR) in GC cells. Moreover, a dual-luciferase reporter gene assay was used to verify the relationship between linc00467 and miR-7-5p. Results showed that the expression of linc00467 was overexpressed in GC. Linc00467 silencing decreased the GC cell proliferation, migration, and invasion. With mRNA verification and combined previous research, linc00467 directly regulated the miR-7-5p expression and downstream EGFR expression. Inhibited miR-7-5p could restore cell function, EGFR expression of GC cells when linc00467 knockdown occurs. Altogether, linc00467 directly regulates the miR-7-5p and EGFR signaling pathway to promote GC proliferation, migration, and invasion.

Novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives suppress cancer via inducing PI3K/Akt/mTOR-dependent autophagy.

Honokiol is a bioactive biphenolic component derived from Magnoliae officinalis Cortex (known as "Hou Po" in Chinese), a traditional Chinese herbal medicine. A series of novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives were synthesized and tested for anticancer activity against seven human cancer cell lines in this study. Among all derivatives, 8a had the most potent cytotoxic effect on all tested cancer cells, with IC50 values ranging from 1.62 ± 0.19 to 4.61 ± 0.51 µM, which were 10.38-34.36 folds more potent than the parental honokiol (IC50 values of 30.96 ± 1.81-55.67 ± 0.31 µM). On A549, HCT116, and MDA-MB-231 cell lines, 8a demonstrated 5.69-fold, 5.65-fold, and 4.83-fold greater cytotoxicity than cisplatin, respectively. Compound 8a also had higher selectivity (SI values of 8.41-49.38) towards seven cancer cell lines over the normal cell lines than cisplatin (SI values of 1.24-2.52). The analysis of structure-activity relationships (SARs) revealed that honokiol derivatives bearing 1,3,4-thiadiazoles (8a-j) possessed stronger anticancer activity than those containing 1,3,4-oxadiazoles. Further mechanistic investigation indicated that 8a induced cytotoxic autophagy in cancer cells in a time- and dose-independent manner via suppressing the PI3K/Akt/mTOR pathway. Molecular docking suggested that 8a could bind to the PI3Kα active sites. Additionally, 8a inhibited the migration and invasion of A549 and MDA-MB-231 cancer cells.

Cough Inhibition Activity of Schisandra chinensis in Guinea Pigs.

Chronic cough is very common in respiratory clinics, and no effective drugs are available. Schisandra chinensis (Turcz.) Baill. (S. chinensis), an important traditional Chinese medicine, has been extensively prescribed for patients with a persistent cough. Preliminary research indicated that 95% ethanol extracts (EE) of S. chinensis showed remarkable antitussive activity in guinea pigs exposed to cigarette smoke (CS). To find out the antitussive ingredients of S. chinensis, EE was divided into four fractions according to the polarity: petroleum ether extract (PEE), ethyl acetate extract (ECE), n-butyl alcohol extract, and residue extract. The antitussive, antioxidant, and anti-inflammatory effects of the four fractions were evaluated in a guinea pig model of cough hypersensitivity induced by CS exposure. Eighteen main constituents of the two effective fractions, PEE and ECE, were identified using ultra-high-pressure liquid chromatography electronic spray ion time-of-flight mass spectrometry. The cough inhibition activities of compound 1, 3, 9, 10, 17 were evaluated on citric acid induced acute cough guinea pigs. The results showed that the antitussive activity of EE was almost all contained in PEE and ECE. The 16 major peaks in PEE were identified as 15 lignans (1-12 and 14-16) and 1 triterpene (compound 13), and 3 major peaks (1, 17, and 18) in ECE were also identified as lignans. Three doses of five compounds brought about a significant decrease in number of cough efforts (P < .01), and the cough inhibition rates were between 40.9% and 85.1%. Therefore, lignans are the antitussive ingredients of S. chinensis.

Non-classical cardenolides from Calotropis gigantea exhibit anticancer effect as HIF-1 inhibitors.

Six new non-classical cardenolides (1-6), and seventeen known ones (7-23) were isolated from Calotropis gigantea. All cardenolides showed inhibitory effect on hypoxia inducible factor-1 (HIF-1) transcriptional activity with IC50 of 8.85 nM-16.69 µM except 5 and 7. The novel 19-dihydrocalotoxin (1) exhibited a comparable HIF-1 inhibitory activity (IC50 of 139.57 nM) to digoxin (IC50 of 145.77 nM), a well-studied HIF-1 inhibitor, and 11, 12, 14, 16 and 19 presented 1.4-15.4 folds stronger HIF-1 inhibition than digoxin. 1 and 11 showed a dose-dependent inhibition on HIF-1α protein, which led to their HIF-1 suppressing effects. Compared with LO2 and H9c2 normal cell lines, both 1 and 11 showed selective cytotoxicity against various cancer cell lines including HCT116, HeLa, HepG2, A549, MCF-7, A2780 and MDA-MB-231. Moreover, a comprehensive structure-activity relationship was concluded for these non-classical cardenolides as HIF-1 inhibitors, which may shed some light on the rational design and development of cardenolide-based anticancer drugs.

Semisynthesis of novel magnolol-based Mannich base derivatives that suppress cancer cells via inducing autophagy.

Magnolol, a natural bioactive neolignan, was found in the bark of a traditional Chinese medicine Magnoliae officinalis ("Hou Po" in Chinese). In this study, thrity-two magnolol-based Mannich base derivatives 3a-p and 4a-p were synthesized, and evaluated for their anti-proliferative activities against a panel of human tumor cell lines (T47D, MCF-7, Hela and A549). Among all derivatives, compound 3p displayed the most potent antiproliferative activity against T47D, MCF-7 and Hela cell lines with IC50 values of 0.91, 3.32 and 1.71 µM, respectively. Compared with the parental magnolol and the positive drug cisplatin, 3p exhibited up to 76.1-fold and 10.3-fold enhancement of cytotoxic effect on T47D cancer cells, respectively. Mechanism study revealed that the most potent derivative 3p suppressed cancer cells via inducing autophagy. Moreover, 3p also possessed suppressive effects on migration of T47D and Hela cancer cells. In addition, some interesting structure-activity relationships (SARs) were also summarized.

Novel ginsenoside derivative 20(S)-Rh2E2 suppresses tumor growth and metastasis in vivo and in vitro via intervention of cancer cell energy metabolism.

Increased energy metabolism is responsible for supporting the abnormally upregulated proliferation and biosynthesis of cancer cells. The key cellular energy sensor AMP-activated protein kinase (AMPK) and the glycolytic enzyme alpha-enolase (α-enolase) have been identified as the targets for active components of ginseng. Accordingly, ginseng or ginsenosides have been demonstrated with their potential values for the treatment and/or prevention of cancer via the regulation of energy balance. Notably, our previous study demonstrated that the R-form derivative of 20(R)-Rh2, 20(R)-Rh2E2 exhibits specific and potent anti-tumor effect via suppression of cancer energy metabolism. However, the uncertain pharmacological effect of S-form derivative, 20(S)-Rh2E2, the by-product during the synthesis of 20(R)-Rh2E2 from parental compound 20(R/S)-Rh2 (with both R- and S-form), retarded the industrialized production, research and development of this novel effective candidate drug. In this study, 20(S)-Rh2E2 was structurally modified from pure 20(S)-Rh2, and this novel compound was directly compared with 20(R)-Rh2E2 for their in vitro and in vivo antitumor efficacy. Results showed that 20(S)-Rh2E2 effectively inhibited tumor growth and metastasis in a lung xenograft mouse model. Most importantly, animal administrated with 20(S)-Rh2E2 up to 320 mg/kg/day survived with no significant body weight lost or observable toxicity upon 7-day treatment. In addition, we revealed that 20(S)-Rh2E2 specifically suppressed cancer cell energy metabolism via the downregulation of metabolic enzyme α-enolase, leading to the reduction of lactate, acetyl-coenzyme (acetyl CoA) and adenosine triphosphate (ATP) production in Lewis lung cancer cells (LLC-1), but not normal cells. These findings are consistent to the results obtained from previous studies using a similar isomer 20(R)-Rh2E2. Collectively, current results suggested that 20(R/S)-Rh2E2 isomers could be the new and safe anti-metabolic agents by acting as the tumor metabolic suppressors, which could be generated from 20(R/S)-Rh2 in industrialized scale with low cost.

Characterization of covalent protein modification by triclosan in vivo and in vitro via three-dimensional liquid chromatography-mass spectrometry: New insight into its adverse effects.

Triclosan (TCS), an antimicrobial agent widely used in personal care products and ubiquitously exists in environment, has drawn increasing concern due to its potential to exert multiple adverse effects, ranging from endocrine disruption to carcinogenesis. However, the mechanism of these adverse effects is still not fully elucidated. More and more studies have shown that chemical reactive metabolites (RMs) covalently binding to proteins is a possible reason for these adverse effects, but there is still a lack of appropriate methods to predict or evaluate these adverse effects due to the extremely low abundance of the modified proteins in complex biological samples. In this study, we attempted to address this problem and investigate the possible mechanism of TCS adverse effects by a shotgun proteomics approach based on three-dimensional-liquid chromatography-mass spectrometry (3D-LC-MS). First, the in vitro incubation with model amino acids and protein in microsomes showed that TCS could react with cysteine residue of proteins through 3 types of RMs. Then, a 3D-LC-MS approach was developed to sensitively determine the low abundant modified proteins, which resulted in the identification of 45 TCS-modified proteins, including albumin, haptoglobin and NR1I2, in rats. STRING analysis indicated that these modified proteins mainly were involved in reproductive and development system, endocrine and immune system, and carcinogenesis, which were in accord with the main reported TCS-induced adverse effects and suggested that the covalent modification of TCS RMs for proteins might affect their activities and functions, thus inducing serious adverse effects. This study provided a new insight into the mechanism of TCS adverse effects and may serve as a valuable method to predict or evaluate adverse effects of ubiquitous chemicals.

Natural Value of Böhler's Angle in Normal Chinese Population.

OBJECTIVE: To determine the value of Böhler's angle (BA) in a group of Chinese people, analyze possible factors that influence it, and compare BA with that in previous literature. METHODS: A total of 143 cases, aged from 4 to 79 years, were enrolled in the study, including 64 males and 79 females (79 left feet and 64 right feet). Radiographs were independently measured by six observers. Age, sex, body side, subtalar joint congruity (STJC), and X-beam obliquity (TT) were recorded. The database was assessed based on intraobserver agreement, data distribution, the randomness of case selection, and the ratio equality of binomial variables. Then, the normal value of BA was established, as well as the correlation between BA and other parameters. RESULTS: In the present study, the interobserver reliability of BA, STJC, and TT was excellent. The BA data revealed a normal distribution, and the randomness of case selection was verified for age, sex, and body side. The ratio of sex and body side was equal. Homogeneity of variance was observed when comparing the value of BA between different groups. The value of BA was 31.6° ± 5.19° (range, 20.08°-47.19°), which was not related to age, sex, body side, and minor X-ray beam obliquity. BA application was not suitable for individuals younger than 10 years. The mean value of BA in this study was not identical with those in previous reports. This demonstrated that BA varies for different races. CONCLUSION: For Chinese people, 30° to 33° is recommended as the target value of BA for calcaneal fracture reduction, except in children under 10 years of age.

Identification of an IKKß inhibitor for inhibition of inflammation in vivo and in vitro.

Targeting on the IKKß to discover anti-inflammatory drugs has been launched for ten years, due to its predominant role in canonical NF-κB signaling. In the current study, we identified a novel IKKß inhibitor, ellipticine (ELL), an alkaloid isolated from Ochrosia elliptica and Rauvolfia sandwicensis. We found that ELL reduced the secretion and mRNA expression of TNF-α and IL-6 and decreased the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in bone marrow derived macrophages (BMDMs) stimulated with LPS. In coincided with the results, ELL suppressed PGE2 and NO production in BMDMs. Underlying mechanistic study showed that ELL inhibited IκBα phosphorylation and degradation as well as NF-κB nuclear translocation, which was attributed to suppression of IKKα/ß activation. Furthermore, kinase assay and binding assay results indicated that ELL inhibited IKKß activity via directly binding to IKKß and in turn resulted in suppression of NF-κB signaling. To identify the binding sites of ELL on IKKß, IKKßC46A plasmid was prepared and the kinase assay was performed. The results demonstrated that the inhibitory effect of ELL on IKKß activity was impaired in the mutation, implying that anti-inflammatory effect of ELL was partially attributed to binding on cysteine 46. Furthermore, ELL up-regulated LC3 II expression and reduced p62 expression, suggesting that autophagy induction contributed to the anti-inflammatory effect of ELL as well. In coincided with the in vitro results, ELL increased the survival and antagonized the hypothermia in the mice with LPS-induced septic shock. Consistently, ELL reduced TNF-α and IL-6 production in the serum of the mice treated with LPS. Collectively, our study provides evidence that ELL is an IKKß inhibitor and has potential to be developed as a lead compound for treatment inflammatory diseases in the future.