Publications by authors named "Huanghe Yu"

11 Publications

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Biomimetic Hybrid Membrane-Coated Xuetongsu Assisted with Laser Irradiation for Efficient Rheumatoid Arthritis Therapy.

ACS Nano 2021 Dec 29. Epub 2021 Dec 29.

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.

Rheumatoid arthritis (RA) is a systemic autoimmune disease underlying a cascade of chronic inflammatory processes. Over the past decades, the response rate of effective RA treatments has remained scarce despite numerous advancements in the current therapeutic interventions, owing largely to the associated off-target adverse events and poor accumulation in the inflamed joints. Recently, there is a high interest in the development of targeted drug delivery system by using nanotechnology, as it can provide a handle to improve the therapy efficacy of RA. Here, multifunctional [email protected]@[email protected] nanoparticles (HRPS NPs) are developed by loading schisanlactone E (SE, also called with xuetongsu), an anti-RA compound isolated from Tujia ethnomedicine , into Prussian blue nanoparticles (PB NPs) and further camouflage of RBC-RAFLS hybrid membrane with HA modification onto [email protected] NPs (PS NPs). We demonstrated that the modification of RFM makes PB NPs ideal decoys for targeting inflammatory mediators of arthritis due to the homing effects of the parental cells. Moreover, the encapsulation of RFM on the [email protected] NPs extended the blood circulation time and improved its targeting ability, which accordingly achieved optimal accumulation of SE in arthritic rat paws. and assay demonstrated the outstanding performance of HRPS NPs for synergistic chemo-/photothermal therapy of RA without side effects to healthy tissues. Molecular mechanism exploration indicated that the ultrastrong inhibition of synovial hyperplasia and bone destruction was partly suppressing NF-κB signaling pathway and the expression of matrix metalloproteinases. In summary, the nanodrug delivery system showed controllable release behavior, targeted accumulation at arthritic sites and systemic regulation of immunity, hence improved therapeutic efficacy and clinical outcomes of the disease without attenuating safety.
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http://dx.doi.org/10.1021/acsnano.1c07556DOI Listing
December 2021

Sesquiterpenes from Kadsura coccinea attenuate rheumatoid arthritis-related inflammation by inhibiting the NF-κB and JAK2/STAT3 signal pathways.

Phytochemistry 2022 Feb 24;194:113018. Epub 2021 Nov 24.

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China. Electronic address:

The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named "heilaohu", having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC value of 9.37 μM. In the same line, nine compounds exhibited significant inhibition effects against TNF-α and IL-6 release in the LPS-induced RAW264.7 cells with IC values ranging between 1.03 and 10.99 μM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF-kB and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies.
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http://dx.doi.org/10.1016/j.phytochem.2021.113018DOI Listing
February 2022

Dibenzocyclooctadiene lignans from Kadsura coccinea alleviate APAP-induced hepatotoxicity via oxidative stress inhibition and activating the Nrf2 pathway in vitro.

Bioorg Chem 2021 10 19;115:105277. Epub 2021 Aug 19.

TCM and Ethnomedicine Innovation & Development International Laboratory, Atta-ur-Rahman Belt and Road Tradition Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, People's Republic of China; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address:

Phytochemical investigation on the roots of Kadsura coccinea led to the isolation five previously unknown dibenzocyclooctadiene lignans, named heilaohusuins A-E (1-5). Their structures determined by NMR spectroscopy, HR-ESI-MS, and ECD spectra. Hepatoprotection effects of a series of dibenzocyclooctadiene derivatives (1-68) were investigated against acetaminophen (APAP) induced HepG2 cells. Compounds 2, 10, 13, 21, 32, 41, 46, and 49 showed remarkable protective effects, increasing the viabilities to > 52.2% (bicyclol, 52.1 ± 1.3%) at 10 μM. The structure-activity relationships (SAR) for hepatoprotective activity were summarized, according to the activity results of dibenzocyclooctadiene derivatives. Furthermore, we found that one new dibenzocyclooctadiene lignan heilaohusuin B attenuates hepatotoxicity, the mechanism might be closely correlated with oxidative stress inhibition via activating the Nrf2 pathway.
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http://dx.doi.org/10.1016/j.bioorg.2021.105277DOI Listing
October 2021

Anti-gastric cancer activity and mechanism of natural compound "Heilaohulignan C" isolated from Kadsura coccinea.

Phytother Res 2021 Jul 21;35(7):3977-3987. Epub 2021 Jun 21.

TCM and Ethnomedicine Innovative & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China.

In this research, we analyzed the antitumor activity of one new compound Heilaohulignan C (B-6) on the human gastric carcinoma cells. MTT, cell migration, Calcein AM/Propidium Iodide (PI), and flow cytometry in BGC-823 cell line (gastric tumor). Western blot was utilized to distinguish the protein level. Xenografts nude mice were used for in vivo anticancer analysis. H&E staining and laboratory investigation was accomplished for toxicity study. MTT test demonstrated the cytotoxicity of BGC-823 cells, Calcein AM/Propidium Iodide (PI) examine indicated increment dead cells proportion with a high dose of B-6, Flow cytometry (FACS) measure showed that B-6 influenced gastric cancer cells by initiating apoptosis. Western blot analysis confirmed that (B-6) decrease the level of Bcl-2 and increase the level of p53, Bax, and cleaved Caspase-3, this confirms that the B-6 doing the apoptosis through caspase and cytochrome C apoptotic pathways. Also, B-6 particularly decline the tumor volume and tumor size in the xenograft mice. H&E staining additionally supports that B-6 does not have any toxic impact on the normal tissues. This research supports that B-6 have pharmacological activity against gastric cancer, by p53 and mitochondrial dependent apoptotic pathway, and have no toxicity on normal tissues.
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http://dx.doi.org/10.1002/ptr.7114DOI Listing
July 2021

Transcriptomic and metabonomic profiling reveal the anti-obesity effects of Chikusetsusaponin V, a compound extracted from Panax japonicus.

J Pharm Pharmacol 2021 Mar;73(1):60-69

TCM and Ethnomedicine Innovation & Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, PR China.

Objectives: To explore the in vivo anti-obesity effect of chikusetsusaponin V and explore the underlying mechanism by transcriptomic and metabonomic methods.

Methods: The physiological parameters of high-fat-diet induced obese mice administered with or without 25 mg/kg and 100 mg/kg of chikusetsusaponin V by gavage for 16 weeks were recorded. In addition, the RNA-sequencing and UHPLC-Q-TOF techniques were applied to obtain the transcriptomic and metabolomic profiling, respectively.

Key Findings: Chikusetsusaponin V could significantly alleviate the high-fat-diet induced increase in the weight of the whole body and obesity-related organs or tissues, and ameliorate the lipid content in the blood, the lipid accumulation in the livers, as well as the hypertrophy of the fat tissues. Importantly, transcriptomic results revealed that more than 30 genes involved in the pathway which closely associates with obesity, were significantly altered. Moreover, metabolomic data indicated the key differential metabolites enriched in the pathways such as the activated protein kinase signaling pathway which is a vital mediator of obesity and other processes.

Conclusions: The integrative analysis highlighted that chikusetsusaponin V significantly influenced the activated protein kinase signaling pathway at both transcriptomic and metabolomic levels, thereby exerting anti-obesity effects.
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http://dx.doi.org/10.1093/jpp/rgaa029DOI Listing
March 2021

Advancement of Natural Compounds as Anti-rheumatoid Arthritis Agents: A Focus on Their Mechanism of Actions.

Mini Rev Med Chem 2021 ;21(19):2957-2975

TCM and Ethnomedicine Innovation and Development International Laboratory, Academician Atta-ur-Rahman Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by infiltration of inflammatory cells, synovial hyperplasia, pannus formation and bone destruction. RA is associated with high incidence of disability worldwide. Although several anti-RA agents are available in the market, clinical use of these drugs is limited due to their severe side effects. Several studies are currently exploring new anti-rheumatic drugs which are more effective and have fewer side effects. Notably, natural products with anti-RA effect have been identified and studies have reported the underlying molecular mechanisms of action of the novel and known compounds. This review explored naturally occurring known and novel compounds that have anti-RA activity. Further, the compounds are classified based on their molecular mechanisms of action as anti-RA agents. In addition, the safety of compounds from natural sources is compared with that of conventional drugs. In addition, clinical trials for anti-RA compounds isolated from natural plant sources were summarized in this manuscript.
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http://dx.doi.org/10.2174/1389557521666210304112916DOI Listing
January 2021

Endogenous Cys-Assisted [email protected] Nanoprobe for Real-Time Monitoring of Dynamic Change in GSH Levels Regulated by Natural Drug.

Anal Chem 2020 01 30;92(2):1988-1996. Epub 2019 Dec 30.

College of Biology , Hunan University , Changsha , Hunan 410082 , P. R. China.

Glutathione (GSH) levels are closely related to the homeostasis of redox state which directly affects human disease occurrence by regulating cell apoptosis. Hence, real-time monitoring of dynamic changes in intracellular GSH levels is urgently needed for disease early diagnosis and evaluation of therapy efficiency. In this study, an endogenous cysteine (Cys)-assisted detection system based on [email protected] and reduced graphene oxide (rGO) with high sensitivity and specificity was developed for GSH detection. Compared with GSH, [email protected] with weaker affinity and bonding force was quite easier to extrude from the rGO surface when competing against GSH, leading to the obvious change in fluorescence signal. This phenomenon was termed as "a crowding out effect". Furthermore, the presence of Cys can improve GSH assay sensitivity by enhancing the quenching efficiency of rGO on the [email protected] In vitro assay indicated that the efficiency of fluorescence recovery was positively related with GSH concentration in the range from 0 to 10 mM. In addition, the method was employed for real-time monitoring of the dynamic changes in GSH levels regulated by natural drugs. The imaging results showed that the natural compound (C3) can downregulate GSH levels in HepG2 cells, which was accompanied by reactive oxygen species (ROS) release and apoptosis induction. Finally, the method was used to monitor the change of GSH levels in serum samples with chronic hepatitis B (CHB) infection. The results demonstrated that the occurrence and development of CHB may be positively correlated with GSH levels to some extent. Overall, the above results demonstrate the potential application of this new nanosystem in anticancer natural drug screening and clinical assay regarding GSH levels.
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http://dx.doi.org/10.1021/acs.analchem.9b04374DOI Listing
January 2020

New Lignans from roots of Kadsura coccinea.

Fitoterapia 2019 Nov 16;139:104368. Epub 2019 Oct 16.

TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, People's Republic of China. Electronic address:

Four new dibenzocyclooctadiene lignans, named heilaohusus A-D (1-4), one new arylnaphthalene lignan named heilaohusu E (5), and seven known analogues (6-12) were isolated from the roots of Kadsura coccinea. Their structures and configurations were elucidated by a combination of HR-ESI-MS, H NMR, C NMR, HSQC, HMBC, NOESY and CD spectra. Among the known compounds, compounds 6 and 8-12 were isolated from this plant for the first time. All of compounds were evaluated for their cytotoxicity activities, compounds 3, 6 and 7 showed weak cytotoxicity against four human cancer cell lines (HepG-2, HCT-116, BGC-823 and Hela) with IC values range from 13.04 to 21.93 μM. Compounds 1 and 7 demonstrated potential anti-RA (rheumatoid arthritis) activity against RA-FLS cell line with IC values of 14.57 and 11.70 μM, respectively.
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http://dx.doi.org/10.1016/j.fitote.2019.104368DOI Listing
November 2019

Two new alkaloids isolated from traditional Chinese medicine Binglang the fruit of Areca catechu.

Fitoterapia 2019 Oct 24;138:104276. Epub 2019 Jul 24.

TCM and Ethnomedicine Innovation & Development International Laboratory, Academician Atta-ur-Rahamn Belt and Road Traditional Medicine Research Center, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China. Electronic address:

Binglang, the fruit of Areca catechu L, has a long history as an important Chinese herbal medicine. Two new alkaloids (1 and 2), along with forty-one known compounds (3-43) were isolated from the dried fruit of Areca catechu L. The structures were elucidated on basis of the IR, UV, MS and 1D, 2D NMR spectroscopic data. Compounds 26 and 33 showed weak cytotoxicity against human gastric cancer cell line (BGC-823) with IC of 15.91 μM and 20.13 μM, respectively.
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http://dx.doi.org/10.1016/j.fitote.2019.104276DOI Listing
October 2019

Kadsura heteroclita stem suppresses the onset and progression of adjuvant-induced arthritis in rats.

Phytomedicine 2019 May 25;58:152876. Epub 2019 Feb 25.

TCM and Ethnomedicine Innovation & Development International Laboratory, and Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China. Electronic address:

Background: Rheumatoid arthritis (RA) is a chronic autoimmune diseased state, characterized by hyperplasia of the synovial membrane, degradation of cartilage, and bone erosion of diarthrodial joints. Kadsura heteroclita (Roxb) Craib (Schizandraceae), a traditional Tujia ethnomedicine called Xue Tong in China, has been long used for the prevention and treatment of rheumatic and arthritic diseases, especially in the southern China. This study aimed to evaluate anti-arthritic effects of the ethanol extract of Kadsura heteroclita stems (KHS) on complete Freund's adjuvant (CFA)-induced arthritis (AIA) in rats, as well as to explore the underlying mechanisms of anti-arthritis.

Methods: AIA was established in male Sprague-Dawley (SD) rats as described previously, and animals were daily treated by gavage with KHS ethanol extract (200, 400, or 800 mg/kg) or vehicle (0.3% CMCNa) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical parameters. At the end of experiments, tissue swelling and bone destruction of the hind paws were assessed by computed tomography (CT) and histopathological analyses. Serum levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-17A and IL-17F were measured by ELISA, and protein expression of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitor of MMP-1 (TIMP-1) were detected by Western blot.

Results: Treatment with KHS dose-dependently inhibited paw swelling and reduced arthritis scores of AIA rats. CT images displayed that KHS remarkably protected AIA rats from tissue swelling and bone erosion of joints. Histopathological analyses revealed that KHS markedly reduced inflammatory cell infiltration, synovial proliferation, and the formation of pannus in the ankle joints of AIA rats. KHS was found to significantly suppress the production of TNF-α, IL-1 β, IL-6, IL-17A and IL-17F, inhibited the protein expression of MMP-1 and MMP-3, and elevated the protein expressions of TIMP-1.

Conclusion: KHS demonstrates potential anti-arthritic effects via inhibiting pivotal mediators of inflammation and cartilage destruction. This study strongly supports identification and isolation of active fractions of KHS which would be a potential candidate for further investigation as a new anti-arthritic botanical drug.
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http://dx.doi.org/10.1016/j.phymed.2019.152876DOI Listing
May 2019

Recent Development on Anti-Obesity Compounds and their Mechanisms of Action: A Review.

Curr Med Chem 2020 ;27(21):3577-3597

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Drug Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.

Obesity, associated with a series of complications such as diabetes, hypertension, and heart disease, is a great threat to human health and leads to increased morbidity and mortality. Despite the presence of anti-obesity agents on the market, the application of these drugs is limited because of their typical side effects. More effective and safe weight-loss drugs are being pursued by many researchers, correspondingly, growing small molecules and natural products with anti-obesity effects have been identified and the molecular mechanisms underlying the action of the novel and known compounds have at least partially been revealed. Therefore, the field does witness great progress year by year. In this review, we intend to provide a comprehensive and updated view on the known and novel compounds which possess anti-obesity effects and further classify them according to the molecular mechanisms of their actions in regulating the major anti-obesity pathways.
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http://dx.doi.org/10.2174/0929867326666190215114359DOI Listing
August 2020
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