New Cadinane Sesquiterpenes from the Stems of Kadsura heteroclita.

As part of our continual efforts to exploit 'Tujia Ethnomedicine' for their pharmacophoric functionalities, we herein investigated Kadsura heteroclita collected from a deep Wulin mountain area in northern Hunan province. The current study resulted in the isolation of three new sesquiterpenes: 6α,9α,15-trihydroxycadinan-4-en-3-one (1), (+)-3,11,12-trihydroxycalamenene (2), (-)-3,10,11,12-tetrahydroxy-calamenene (3), along with four known sesquiterpenes (4-7), and a cytochalasin H (8). Their chemical structures were elucidated by 1D-, and 2D-NMR spectroscopy, and HRESI-MS, CD spectrometry. The antioxidant, and cytotoxic activities of the compounds were evaluated. Compound 8 exhibited a strong antioxidant effect with an IC50 value of 3.67 µM on isolated human polymorphonuclear cells or neutrophils.

Quantitative and qualitative determination of LiuweiDihuang preparations by ultra high performance liquid chromatography in dual-wavelength fingerprinting mode and random forest.

The classical traditional Chinese formulation LiuweiDihuang, shown to have clinical efficacy for "nourishing kidney-yin" in traditional Chinese medicine, has been used for thousands of years in China. Little attention, however, has been paid to quality control methods for this formulation. Hence, a rapid and sensitive analytical technique is urgently needed for the evaluation of LiuweiDihuang preparations to assess its quality and pharmacological functionality. In this study, an ultra high performance liquid chromatography dual-wavelength method was developed to simultaneously determine 11 constituents in LiuweiDihuang preparations. This robust approach provided a fast and comprehensive quantitative determination of the major bioactive markers within LiuweiDihuang preparations. To distinguish four dosage forms of LiuweiDihuang preparations, a random forest technique was applied on the spectrometric fingerprint data obtained. This combination approach of chromatographic techniques and data analyses might serve as a rapid and efficient tool to ensure the quality of LiuweiDihuang preparations and other Chinese medicinal formulations and can support quality control and scientific research into the pharmacological potential for these formulations.

Cyclocarya paliurus (Batalin) Iljinskaja: Botany, Ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) also known as Sweet tea tree, Money tree, Money willow, green money plum, mountain willow and shanhua tree, is a native rare monocotyledonous plant in Southern China. It possesses numerous traditional benefits, including clearing heat, detoxification, producing saliva, slake thirst, anti-inflammatory, insecticidal, dispelling wind and relieving itching. It is also effective in preventing and treating diabetes, hypertension, hyperlipidemia, dizziness and swelling and pain, as well as reducing cholesterol, and modulating the functions of the immune system. The stem, leaves and bark of this plant are all medicinal parts, but the leaves have the highest research value. AIM OF THE STUDY: This article summarized the plant's botanical description, distribution, ethnopharmacology, phytochemical profiles and pharmacological for the first time, to provide possible directions for future development and research in brief. MATERIAL AND METHODS: The literature for this current manuscript was obtained from reports published from 1992 to May 2021 in diverse databases such as the China Knowledge Resource Integrated databases (CNKI), SciFinder, Google Scholar, Baidu Scholar, Elsevier and Pub-Med. The domestic and foreign references published about C. paliurus over recent years were collected, analyzed and summarized. RESULTS: The botanical characteristics of the fruits of C. paliurus are unique in having a central nutlet surrounded by a circular wing to distinguish the living genera of Juglandaceae. In traditional medicine, C. paliurus leaves are used by the local people of Southern China to make tea to prevent diabetes. More than 210 compounds have been isolated from C. paliurus. Among them, the characteristic 3,4-seco-dammaranes accounted for the most. Other compounds include dammarane tetracyclic triterpenoids, various pentacyclic triterpenoids, flavonoids, isosclerones, phenolic derivatives and polysaccharides. The plant extracts and compounds have been reported to exert various pharmacological activities, such as anti-hyperglycemic, anti-hyperlipidemic, anti-cancer, cytotoxic, anti-oxidative, anti-inflammatory, hepatoprotective, and anti-microbial activities. CONCLUSIONS: Comprehensive literature analysis shows that C. paliurus extract and its compounds have a variety of biological activities for the treatment of various diseases. The current modern pharmacology research is mostly related to the records of ethnic pharmacology, mainly in vitro research, relatively few in vivo research. Therefore, future studies should focus on this aspect. In addition, we also would like to recommend further research should concentrate on toxicity studies and quality control of C. paliurus to fill the study gap, as well as to provide theoretical support for the further development of the potential functions and clinical applications of the plant.

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

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 HA@RFM@PB@SE nanoparticles (HRPS NPs) are developed by loading schisanlactone E (SE, also called with xuetongsu), an anti-RA compound isolated from Tujia ethnomedicine xuetong, into Prussian blue nanoparticles (PB NPs) and further camouflage of RBC-RAFLS hybrid membrane with HA modification onto PB@SE 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 PB@SE NPs extended the blood circulation time and improved its targeting ability, which accordingly achieved optimal accumulation of SE in arthritic rat paws. In vitro and in vivo 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 via 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.

New dibenzocyclooctadiene lignan from stems of Kadsura heteroclita.

Kadsura heteroclita Roxb. Craib. (Schisandraceae), is a vine plant mainly distributed in southwest part of China. A new dibenzocyclooctadiene lignan, kadsulignan W (1), along with eleven known lignans (2-12) were isolated from chloroform soluble fraction of stems of Kadsura heteroclita. The structure of new lignan was elucidated by extensive spectroscopic techniques, namely one- and two-dimensional NMR spectroscopy, and HRESI-MS analysis. The absolute configuration of the biphenyl ring in the new dibenzocyclooctadiene lignan was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated on human isolated neutrophils, and compounds 5, 8, 9, and 10 were found to be strongly active with the IC50 of 36.68, 34.41, 35.97, and 33.65 µM, respectively. Furthermore, compound 8 was also found to be cytotoxic against human gastric cancer cells (BGC 823), and human cervical cancer cell lines (HeLa) with the IC50 values of 11.0, and 23.8 µM, respectively.

Simultaneously qualitative and quantitative analysis of the representative components in Kadsura heteroclita stem by UHPLC-Q-Orbitrap HRMS.

Kadsura heteroclita (Roxb) Craib stem (KHS) is a medicinal plant used for the treatment of rheumatism arthritis diseases in Tujia ethnomedicine. Thus far, the complex chemical compositions in KHS are not clear, and the levels of the major compounds in KHS are not well understood. In this study, a novel UHPLC-Q-Orbitrap HRMS method was established for the simultaneous quali-quantitative analysis of KHS. A total of 204 compounds were identified, including triterpenoids, lignans, sesquiterpenes, fatty acids, phenolic acids, and flavonoids, more than 100 of which were first discovered in KHS. Using the same method, 12 representative bioactive components were successfully quantified. The method was fully validated by linearity, LOD, LOQ, precision, stability, recovery, and matrix effects, and it was applied to quantify the 12 representative compounds in 4 batches of KHS. As this method enables retrospective data analysis and has no upper limit to the number of analytes in a single run, it can be applied to quantify more active components of KHS in the future.

Isoflavanquinones from Abrus precatorius roots with their antiproliferative and anti-inflammatory effects.

Phytochemical studies on the root of Abrus precatorius Linn. (Fabaceae), leads towards the identification of four undescribed (abruquinones M, N, O, and P), and seven known abruquinones, (abruquinones A, E, B, F, I, D, and G). Spectroscopic analyses (1D, and 2D NMR, HRESI-MS) were used in elucidating structures of the all compounds. Evaluation of anticancer activities of the isolated isoflavanquinones revealed that abruquinones M, and N showed cytotoxicity against oral CAL-27 (IC50 values 6.48 and 5.26 µM, respectively), and colon (Caco-2) cell lines (IC50 values 15.79 and 10.33 µM, respectively). Abruquinone M also inhibited the growth of lung cancer cells (NCI-H460) with IC50 of 31.33 µM. The isolated isoflavanquiones also showed potent anti-inflammatory potential through phagocyte oxidative burst and pro-inflammatory cytokine TNF-α inhibition in vitro. These findings suggest isoflavanquinones from A. precatorius roots as candidates for further research in cancer treatment.

Schinortriterpenoids from Tujia ethnomedicine Xuetong-The stems of Kadsura heteroclita.

In the present work, we take advantage of the characteristic NMR signal (δC-10 = 96.0-99.9) for guiding the isolation of schinortriterpenoids (SNTs) from n-butanol fraction of stems of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the identification of three unreported 3,4:9,10-disecocycloartane triterpenoids xuetongdilactones A-C and three undescribed SNTs xuetongdilactones D-F, along with two known SNTs, namely, wuweizidilactone B and micrandilactone B. The structures of the unreported compounds were established based on 1D, and 2D NMR, HRESIMS, and ECD spectroscopic data analysis. The absolute stereochemistry of xuetongdilactone A was determined by X-ray diffraction analysis along with ECD calculation. The antioxidant and cytotoxic activities were evaluated for all the isolated compounds.

Triterpenoids from stems of Kadsura heteroclita.

In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1-6), along with five known triterpenoids (7-11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 µM.

Xuetonglactones A-F: Highly Oxidized Lanostane and Cycloartane Triterpenoids From Kadsura heteroclita Roxb. Craib.

Xuetonglactones A-F (1-6), six unreported highly oxidized lanostane- and cycloartane-type triterpenoids along with 22 known scaffolds (7-28) were isolated from the stems of Kadsura heteroclita (Roxb.) Craib. Compared with previous congeners, xuetonglactone A (1), possesses an unprecedented 20,21-α-epoxide, and xuetonglactone D (4) features an unusual 19-α-hydroperoxyl moiety. The structures and the absolute configurations of the compounds were established by extensive one- and two-dimensional NMR, and electronic circular dichroism (ECD) spectroscopic analysis, with those of 1 and 5 confirmed by single-crystal X-ray diffraction technique. Compounds 1 and 2 exhibited inhibition of iNOS activity in LPS-induced macrophages with IC50 values of 22.0, and 17.0 µg/mL, respectively. While compounds 6, 7, 8, and 24 showed potent cytotoxic activities against human cervical cancer cell lines (HeLa) with the IC50 values of 4.0, 5.8, 5.0, and 6.4 µM, and against human gastric cancer cells (BGC 823) with the IC50 values of 2.0, 5.0, 2.5, and 2.0 µM, respectively. Moreover, plausible biogenetic pathways of (1-6) were also proposed.