Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook

Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adverse reactions has hindered the modernization and internationalization of TCM, while attracting increasing attention from around the world. Unlike chemical drugs and biological agents, the difficulties involved in research on the toxicity and safety of TCM mainly include the complexity of its components and the unpredictability of drug–body interactions. Much of TCM, which has overall therapeutic effects, has the typical mechanisms of multiple components, multiple pathways, and multiple targets. While considering the gradualness and unpredictability of TCM toxicity, the ambiguity of toxicants and safe dosage, and individual differences during long-term TCM administration, we have systematically established key techniques for the toxicity assessment of TCM. These techniques mainly include TCM toxicity discovery in an early phase, based on a combination of drug toxicology genomics and metabolomics;methods to identify dose–toxicity relationships in TCM;and integrated techniques for the exploration of TCM interactions, such as fast-screening tests based on drug-metabolizing enzymes and receptor pathways. In particular, we have developed a new technical system for TCM safety evaluation using molecular toxicology, which has been validated well in research on TCM compatibility contraindication, quality control, and allergen discovery. The application of this key technical platform is introduced here in detail. This application includes model organisms, toxicant biomarkers, a magnetic suspension technique, and the application of network toxicology and computational toxicology in research on the toxicity of Fructus toosendan, Semen cassiae, Polygonum multiflorum, and Fructus psoraleae.

Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury

Danhong injection （DHI）, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute isch-emic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery ocdusion, and evaluated the potential mechanisms under-lying its effects. Pretreatment with DHI （0.9 and 1.8 mL/kg） resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upreg-ulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI （1.8 mL/kg） administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.

Neuroprotective effect of panax notoginseng saponins and its main components

Stroke is the third leading cause of death and the first cause of adult disability in industrial countries [1]. It is charicaterized by hemiplegia, hemianopsia, aphasia, mouth askew and sever sequelae. It is considered that an ischemic disease without any specific treatment method and few effective drugs such as tPA (human tissue-type plasminogen activator) and Edarovone with specific therapeutic window will cause a lot of disadvantages if being used inaccurate. Root of Panax notoginseng (PN) which is one of traditional Chinese medicines (TCMs), was first found in “Shennong’s Classic of Materia Medica” around 200 AD. Panax notogineng saponins(PNS) is a multi-components mixture containing ginseng and saponins as the most important bioactive components which are commonly used in clinical treatment. Also, ginseng and saponins form the main components of many herbal medicines in the market, e.g., Xueshuantong injection [2], Xuesaitong injection [3], Xuesaitong soft capsule [4] and so on. The main monomers of Panax notoginseng saponins (PNS) are Ginsenoside-Rb1, Gensenoside-Rg1, Gensenoside-Re, Gensenoside-Rd and Panax notoginseng saponins-R1 [5]. In this review, we found some important points as well as shortcomings that require special consideration. We therefore highlighted the advances in neuro-protection of PNS and its main monomers in the area of experimental research.

Steroidal saponins with anti-inflammatory activity from Tribulus terrestris L.

Objective:Tribulus terrestris L.(T.terrestris)is a highly valuable traditional Chinese medicine used to treat stroke,inflammation,pulmonary fibrosis,liver cancer,and urolithiasis.To identify the basic substance responsible for the anti-inflammatory effect of TST(total saponins of Tribulus),its chemical composition was systematically studied,and its effect of inhibiting nitric oxide generation and the expression of related inflammatory factors were determined.Methods:To separate chemical constituents from T.terrestris by column chromatography.Spectroscopic methods,including 1D and 2D nuclear magnetic resonance spectroscopy(NMR)and mass spectrometry(MS)techniques,were used to elucidate the isolated compounds.The anti-inflammatory activities of TST and several compounds were evaluated in vitro.Results:Fifteen steroidal saponins,including 9 furostanol steroidal saponins(1,2,3,4,5,6,7,8,and 15)and 6 isospirostanol steroidal saponins(9,10,11,12,13,and 14),were isolated from T.terrestris.TST significantly decreased the expression of tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6)in RAW 264.7 cells stimulated by lipopolysaccharides.Compounds 13 and 15 evidently reduced TNF-a expression.Compounds 6,10,12,13,and 15 markedly reduced IL-6 expression.Conclusions:Compounds 1 was a novel furostanol steroidal saponin,named 26-O-b-D-glucopyranosyl-(25R)-5afurostan-12-carbonyl-20(22)-en-3b,26-diol-3-O-{b-D-xylopyranosyl-(1→2)-[b-D-xylopyranosyl-(1→3)]-b-D-glucopyranosyl-(1→4)-[a-L-rhamnopyranosyl-(1→2)]-b-D-galactopyranoside}.Compounds 2 was isolated from the family Zygophyllaceae for the first time,and 5 and 6 were isolated from the Tribulus genus.TST and compounds 6,10,12,13,and 15 exerts antiinflammatory activity.

The effect of iron on the preservation of organic carbon in marine sediments and its implications for carbon sequestration

Marine sediments are the most significant reservoir of organic carbon(OC)in Earth′s surface system.Iron,a crucial component of the marine biogeochemical cycle,has a considerable impact on marine ecology and carbon cycling.Understanding the effect of iron on the preservation of OC in marine sediments is essential for comprehending biogeochemical processes of carbon and climate change.This review summarizes the methods for characterizing the content and structure of iron-bound OC and explores the influencing mechanism of iron on OC preservation in marine sediments from two aspects:the selective preservation of OC by reactive iron minerals(iron oxides and iron sulfides)and iron redox processes.The selective preservation of sedimentary OC is influenced by different types of reactive iron minerals,OC reactivity,and functional groups.The iron redox process has dual effects on the preservation and degradation of OC.By considering sedimentary records of iron-bound OC across diverse marine environments,the role of iron in long-term preservation of OC and its significance for carbon sequestration are illustrated.Future research should focus on identifying effective methods for extracting reactive iron,the effect of diverse functional groups and marine sedimentary environments on the selective preservation of OC,and the mediation of microorganisms.Such work will help elucidate the influencing mechanisms of iron on the long-term burial and preservation of OC and explore its potential application in marine carbon sequestration to maximize its role in achieving carbon neutrality.

Carbon pools and fluxes in the China Seas and adjacent oceans

The China Seas include the South China Sea, East China Sea, Yellow Sea, and Bohai Sea. Located off the Northwestern Pacific margin, covering 4700000 km^2 from tropical to northern temperate zones, and including a variety of continental margins/basins and depths, the China Seas provide typical cases for carbon budget studies. The South China Sea being a deep basin and part of the Western Pacific Warm Pool is characterized by oceanic features; the East China Sea with a wide continental shelf, enormous terrestrial discharges and open margins to the West Pacific, is featured by strong cross-shelf materials transport; the Yellow Sea is featured by the confluence of cold and warm waters; and the Bohai Sea is a shallow semiclosed gulf with strong impacts of human activities. Three large rivers, the Yangtze River, Yellow River, and Pearl River, flow into the East China Sea, the Bohai Sea, and the South China Sea, respectively. The Kuroshio Current at the outer margin of the Chinese continental shelf is one of the two major western boundary currents of the world oceans and its strength and position directly affect the regional climate of China. These characteristics make the China Seas a typical case of marginal seas to study carbon storage and fluxes. This paper systematically analyzes the literature data on the carbon pools and fluxes of the Bohai Sea,Yellow Sea, East China Sea, and South China Sea, including different interfaces(land-sea, sea-air, sediment-water, and marginal sea-open ocean) and different ecosystems(mangroves, wetland, seagrass beds, macroalgae mariculture, coral reefs, euphotic zones, and water column). Among the four seas, the Bohai Sea and South China Sea are acting as CO_2 sources, releasing about0.22 and 13.86–33.60 Tg C yr^(-1) into the atmosphere, respectively, whereas the Yellow Sea and East China Sea are acting as carbon sinks, absorbing about 1.15 and 6.92–23.30 Tg C yr^(-1) of atmospheric CO_2, respectively. Overall, if only the CO_2 exchange at the sea-air interface is considered, the Chinese marginal seas appear to be a source of atmospheric CO_2, with a net release of 6.01–9.33 Tg C yr^(-1), mainly from the inputs of rivers and adjacent oceans. The riverine dissolved inorganic carbon (DIC) input into the Bohai Sea and Yellow Sea, East China Sea, and South China Sea are 5.04, 14.60, and 40.14 Tg C yr^(-1),respectively. The DIC input from adjacent oceans is as high as 144.81 Tg C yr^(-1), significantly exceeding the carbon released from the seas to the atmosphere. In terms of output, the depositional fluxes of organic carbon in the Bohai Sea, Yellow Sea, East China Sea, and South China Sea are 2.00, 3.60, 7.40, and 5.92 Tg C yr^(-1), respectively. The fluxes of organic carbon from the East China Sea and South China Sea to the adjacent oceans are 15.25–36.70 and 43.93 Tg C yr^(-1), respectively. The annual carbon storage of mangroves, wetlands, and seagrass in Chinese coastal waters is 0.36–1.75 Tg C yr^(-1), with a dissolved organic carbon(DOC) output from seagrass beds of up to 0.59 Tg C yr^(-1). Removable organic carbon flux by Chinese macroalgae mariculture account for 0.68 Tg C yr^(-1) and the associated POC depositional and DOC releasing fluxes are 0.14 and 0.82 Tg C yr^(-1), respectively. Thus, in total, the annual output of organic carbon, which is mainly DOC, in the China Seas is 81.72–104.56 Tg C yr^(-1). The DOC efflux from the East China Sea to the adjacent oceans is 15.00–35.00 Tg C yr^(-1). The DOC efflux from the South China Sea is 31.39 Tg C yr^(-1). Although the marginal China Seas seem to be a source of atmospheric CO_2 based on the CO_2 flux at the sea-air interface, the combined effects of the riverine input in the area, oceanic input, depositional export,and microbial carbon pump(DOC conversion and output) indicate that the China Seas represent an important carbon storage area.

Recent advances in persulfate-based advanced oxidation processes for organic wastewater treatment

In recent years,with the emergence of new pollutants,the effective treatment of wastewater has become very important.Persulfate-based advanced oxidation processes have been successfully applied to the treatment of wastewater,such as wastewater containing antibiotics,pharmaceuticals and personal care products,dyes,endocrine-disrupting chemicals,chlorinated organic pollutants,and phenolics,for the degradation of refractory organic contaminants.This paper summarizes the production of sulfate radicals,which can be generated by the activation of persulfate via conventional and emerging approaches.The existing problems of persulfate-based advanced oxidation processes were analyzed in detail,including residual sulfates,coexisting factors(coexisting inorganic anions and natural organic matter),and energy consumption.This paper proposes corresponding possible solutions to the problems mentioned above,and this paper could provide a reference for the application of persulfate-based advanced oxidation processes in actual wastewater treatment.

Ultralow specific ON-resistance high-k LDMOS with vertical field plate

An ultralow specific on-resistance high-k LDMOS with vertical field plate（VFP HK LDMOS） is proposed. The high-k dielectric trench and highly doped interface N＋ layer are made in bulk silicon to reduce the surface field of the drift region in the VFP HK LDMOS. The gate vertical field plate（VFP） pinning in the high-k dielectric trench can modulate the bulk electric field. The high-k dielectric not only provides polarized charges to assist depletion of the drift region, so that the drift region and high-k trench maintain charge balance adaptively,but also can fully assist in depleting the drift region to increase the drift doping concentration and reshape the electric field to avoid premature breakdown. Compared with the conventional structure, the VFP HK LDMOS has the breakdown voltage of 629.1 V at the drift length of 40 μm and the specific on-resistance of 38.4 mΩ·cm^2 at the gate potential of 15 V. Then the power figure of merit is 10.31 MW/cm^2.