High-Performance Hybrid Phototheranostics for NIR-IIb Fluorescence Imaging and NIR-II-Excitable Photothermal Therapy.

Photothermal therapy operated in the second near-infrared (NIR-II, 1000-1700 nm) window and fluorescence imaging in the NIR-IIb (1500-1700 nm) region have become the most promising techniques in phototheranostics. Their combination enables simultaneous high-resolution optical imaging and deep-penetrating phototherapy, which is essential for high-performance phototheranostics. Herein, carboxyl-functionalized small organic photothermal molecules (Se-TC) and multi-layered NIR-IIb emissive rare-earth-doped nanoparticles (NaYF4:Yb,Er,Ce@NaYF4:Yb,Nd@NaYF4, RENP) were rationally designed and successfully synthesized. Then, high-performance hybrid phototheranostic nanoagents (Se-TC@RENP@F) were easily constructed through the coordination between Se-TC and RENP and followed by subsequent F127 encapsulation. The carboxyl groups of Se-TC can offer strong binding affinity towards rare-earth-doped nanoparticles, which help improving the stability of Se-TC@RENP@F. The multilayered structure of RENP largely enhance the NIR-IIb emission under 808 nm excitation. The obtained Se-TC@RENP@F exhibited high 1064 nm absorption (extinction coefficient: 24.7 L g-1 cm-1), large photothermal conversion efficiency (PCE, 36.9%), good NIR-IIb emission (peak: 1545 nm), as well as great photostability. Upon 1064 nm laser irradiation, high hyperthermia can be achieved to kill tumor cells efficiently. In addition, based on the excellent NIR-IIb emission of Se-TC@RENP@F, in vivo angiography and tumor detection can be realized. This work provides a distinguished paradigm for NIR-IIb-imaging-guided NIR-II photothermal therapy and establishes an artful strategy for high-performance phototheranostics.

Photoactive oligomer with D-D'-A-D'-D''-D'-A-D'-D scaffold for high-efficiency NIR-II phototheranostics.

A D-D'-A-D'-D''-D'-A-D'-D type photoactive oligomer (O-BT) based nanoparticles (NPs) were prepared for biomedical application. The O-BT NPs possessed a high extinction coefficient, excellent hyperthermia generation ability, satisfactory NIR-II fluorescence emission, and good batch-to-batch reproducibility, and could be used as high-efficiency phototheranostics for photothermal therapy and NIR-II fluorescence imaging.

Traditional uses, phytochemistry, pharmacology, toxicology, and quality control of Rhododendron dauricum L. leaves: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron dauricum L. is a traditional herb mainly distributed in the northeast China, Mongolia, Korea Peninsula, and Russia Far East. The dried leaves of Rhododendron dauricum L. (LRD), generally known "Man Shan Hong" have been traditionally applied as folk medicines to treat fever, copious phlegm, asthma, acute and chronic bronchitis, sore throat, dysentery, diabetes mellitus, cancer, and hypertension. To date, no comprehensive review on R. dauricum leaves has been published. AIM OF THE STUDY: Recent progresses in traditional use, phytochemistry, pharmacology, toxicology, and quality control of R. dauricum leaves are systematically presented and critically evaluated in order to provide scientifical basis for its reasonable utilization and further study. MATERIALS AND METHODS: All information about R. dauricum leaves were retrieved from internet scientific databases including Sci-Finder, Web of Science, PubMed, CNKI, Google Scholar, Elsevier, Wiley, ACS publications, SpringerLink, and the Chinese Pharmacopoeia between 1970 and 2022. Plant names were validated by "The Plant List" (http://www.theplantlist.org/). RESULTS: So far, 114 structurally diverse compounds have been isolated and identified from LRD, mainly including flavonoids, diterpenoids, triterpenoids, meroterpenoids, phenols, and 54 volatile components were identified from the essential oils of LRD. Among these, flavonoids are considered as characteristic components and major bioactive phytochemicals. The crude extracts and compounds from LRD have been reported to possess broad pharmacological effects including antitussive and expectorant, anti-inflammatory, anti-HIV, antibacterial, and cytotoxic effects, etc. CONCLUSIONS: As a traditional herb medicine, LRD have been used popularly. On the one hand, traditional uses of LRD provide valuable directions for current research; on the other hand, modern phytochemical and pharmacological studies verify the traditional uses to make its reasonable utilization. However, several defects such as active components determination, in vivo and clinical pharmacological evaluation, toxicology assessment, and quality control of LRD need further study.

Diterpenoids from the whole plants of Croton yunnanensis and their bioactivities.

Four new 19-nor-clerodane diterpenoids (1-4), one new 15,16-dinor-ent-pimarane diterpenoid (5) together with four known diterpenoids (6-9) were isolated from whole plants of Croton yunnanensis. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparing their NMR data with those of previously reported compounds. The experimental and calculated electronic circular dichroism data were used to define their absolute configurations. The 1H and 13C NMR spectra of 6 were completely assigned for the first time. All isolated compounds (1-9) were evaluated for their cytotoxic activities against five human cancer cell lines (including SMMC-7721, HL-60, A-549, MCF-7, and SW-480), and anti-inflammatory activities in LPS-induced RAW264.7 macrophages. Crotonyunnan E (5) exhibited selective cytotoxicities against three tumor cell lines, SMMC-7721 (human hepatoma cells, IC50 4.47 ± 0.39 µM), HL-60 (human premyelocytic leukemia, IC50 14.38 ± 1.19 µM), and A-549 (human lung cancer cells, IC50 27.42 ± 0.48 µM), while none of the compounds showed obviously anti-inflammatory activities at 50 µM level.

Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury.

Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.

Four new chemical constituents from Piper pleiocarpum.

Two new polyoxygenated cyclohexenes (1-2), one new benzoate derivative (3), and one new dineolignan (4) together with one known neolignan (5) were isolated from whole plants of Piper pleiocarpum. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. The 13C NMR spectra of the known compound 5 were completely assigned for the first time. All isolated compounds (1-5) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7, and SW-480), Only compound 4 showed inhibitory activity against MCF-7 cell line with IC50 value of 18.24 ± 0.69 µM.

Pleiocarpumlignan A, a new dineolignan from Piper pleiocarpum Chang ex Tseng.

The investigation of chemical constituents from the whole plants Piper pleiocarpum Chang ex Tseng resulted in the isolation of one new dineolignan, pleiocarpumlignan A (1), along with one known benzoate derivative, trans-2,3-diacetoxy-1-[(benzoy1oxy)methyl]-cyclohexa-4,6-diene (2), and two known neolignans (3-4) as (±)-trans-dehydrodiisoeugenol (3), (7R,8R,3'S)-△8'-3',6'-dihydro-3'-methoxy-3,4-methylenedioxy-6'-oxo-8,3',7,O,4'-lignan (4). Their structures were elucidated through extensive spectroscopic analyses including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. All compounds (1-4) were firstly isolated from Piper pleiocarpum Chang ex Tseng. The 13C NMR spectra of 2 were completely assigned for the first time. Cytotoxic activities of these isolated compounds against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7, and SW-480) were evaluated.

A new furofuran lignan from Piper terminaliflorum Tseng.

The chemical investigation of whole plants Piper terminaliflorum Tseng led to the isolation of one new furofuran lignan, 7-methoxyasarinin (1), along with three known amide alkaloids (2-4) as N-3,5-dimethoxy-4-hydroxycinnamoylpyrrole (2), dihydropipercide (3) and 1-[(2E,4E,9E)-10-(3,4-Methylenedioxyphenyl)-2,4,9-undecatrienoyl]pyrrolidine (4). Their structures were elucidated by extensive spectroscopic analyses, including 1D, 2D NMR and HR-ESI-MS, and by comparison with the literature. Compounds (2-4) were isolated from Piper terminaliflorum Tseng for the first time. All isolated compounds (1-4) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7 and SW-480).

Effects of R type and S type ginsenoside Rg3 on DNA methylation in human hepatocarcinoma cells.

Ginsenoside Rg3, a bioactive constituent isolated from Panax ginseng, exhibits antitumorigenic, antioxidative, antiangiogenic, neuroprotective and other biological activities are associated with the regulation of multiple genes. DNA methylation patterns, particularly those in the promoter region, affect gene expression, and DNA methylation is catalyzed by DNA methylases. However, whether ginsenoside Rg3 affects DNA methylation is unknown. High performance liquid chromatography assay, MspI/HpaII polymerase chain reaction (PCR) and reverse transcription­quantitative PCR were performed to assess DNA methylation. It was demonstrated that 20(S)­ginsenoside Rg3 treatment resulted in increased inhibition of cell growth, compared with treatment with 20(R)­ginsenoside Rg3 in the human HepG2 hepatocarcinoma cell line. It was additionally revealed that treatment with 20(S)­ginsenoside Rg3 reduced global genomic DNA methylation, altered cystosine methylation of the promoter regions of P53, B cell lymphoma 2 and vascular endothelial growth factor, and downregulated the expression of DNA methyltransferase (DNMT) 3a and DNMT3b more than treatment with 20(R)­ginsenoside Rg3 in HepG2 cells. These results revealed that the modulation of DNA methylation may be important in the pharmaceutical activities of ginsenoside Rg3.

Stigma receptivity over the lifetime of the hermaphroditic flower of Elsholtzia rugulosa was negatively correlated with pollen viability.

Dichogamy is generally thought to be a mechanism that prevents self-fertilization in flowering plants. This study aims to investigate the relationships between floral age and stigma receptivity, style length and pollen viability, and define how floral characters avoid self-pollination in a gynodioecious Chinese plant, Elsholtzia rugulosa. We assessed the relationships between flower age and style length, stigma receptivity, and pollen viability in E. rugulosa. This species produces 2 forms with plants bearing either hermaphrodite flowers (H) or female flowers (F). Corolla length in F flowers was shorter than the corolla length of H flowers and produced no pollen. H flowers were protandrous, pollen release of H flowers occurred before stigma receptivity. Stigma receptivity was significantly positively correlated with style length in both F flowers and H flowers. Pollen viability in H flowers declined significantly with floral age. Our results suggest that self-pollination in H flowers is likely reduced by dichogamy because stigma receptivity and pollen viability were effectively separated in time. However, because H inflorescences typically have multiple flowers open at the same time means that geitonogamous selfing is not avoided.

Icariin, a natural flavonol glycoside, extends healthspan in mice.

A major goal of aging research now is to find pharmacological manipulations in healthspan extension. Icariin is a flavonol isolated from medicinal herbal tonics. We have previously reported that icariin extended the healthspan of invertebrate models. Here, we showed that long-term treatment with icariin starting at 12months of age extended healthspan and mean lifespan in C57BL/6 mice. In all our assays associated with healthspan, such as behavioral tests and bone density analysis, we found that icariin boosted healthy features in mice. We also presented data indicating that such beneficial effects of icariin were due to at least two mechanisms: reduced oxidative stress indicated by the induction of antioxidant protein superoxide dismutase (SOD) activity and the decrease of oxidative marker malondialdehyde (MDA); maintained the genomic stability indicated by a reduction in DNA double-stranded breaks and down-regulation of DNA damage response genes. Our results indicated that icariin, a safe and widely used natural flavonol, extended healthspan and maintained genomic stability in a mammalian system.

[Effect of compound bushen recipe on chronic fatigue syndrome in C. elegans: an experimental study].

OBJECTIVE: To evaluate the effect of compound bushen recipe (CBR) in improving the survival state of stress and the overall life span in C. elegans by simulating chronic fatigue syndrome (CFS) under various stress states. METHODS: The tolerance and the average survival time of adult larvae against heat stress (35 degrees C), oxidative stress (250 microg/mL juglone), and in vivo Abeta protein toxicity (Abeta(1-42) transgenic mutant CL4176) under the intervention of the high (500 mg/L), middle (250 mg/L), and low (100 mg/L) dose CBR were observed. The effect of CBR on the average live time (at 25 degrees C), movement distance in 20 seconds, the frequency of pharyngeal pump in 30 seconds, and the reproductive capability were assessed. RESULTS: Compared with the control group, the survival time of heat stressed C. elegans could be significantly increased in each CBR group (P < 0.01). The survival time of heat stressed C. elegans could be elongated, the protein toxicity be attenuated, and the live time prolonged in the high and middle dose CBR groups (P < 0.01, P < 0.05).The movement distance and the frequency of pharyngeal pump could also be increased in the high dose CBR group (P < 0.01). There was no statistical difference in the reproductive capability among all groups (P > 0.05). CONCLUSIONS: CBR could significantly enhance the stress capacity of C. elegans against internal and external environment, and prolong their lifespan. It did not interfere their normal production, and also could improve the quality of life, thus laying a foundation for further mechanism studies and pharmacological researches on CBR in preventing and treating CFS.

Icariin promotes self-renewal of neural stem cells: an involvement of extracellular regulated kinase signaling pathway.

OBJECTIVE: To investigate the effects and underlying molecular mechanisms of icariin (ICA) on self-renewal and differentiation of neural stem cells (NSCs). METHODS: NSCs were derived from forebrains of mice embryos by mechanical dissociation into single cell suspension. The self-renewal of NSCs was measured by neurosphere formation assay. The proliferation of NSCs was detected by water-soluble tetrazolium (WST) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Protein expression of neuron-specific marker tubulin-ßIII(TuJ1) and astrocyte-specific marker glial fibrillary acidic protein (GFAP) were measured by immunofluorescence and Western blotting. Using microarray, the differentially expressed genes (DEGs) were screened between NSCs with or without ICA treatment. The signaling pathways enriched by these DEGs and their role in mediating effects of ICA were analyzed. RESULTS: ICA significantly promoted neurosphere formation of NSCs cultured in growth protocol in a dose-dependent manner and achieved the maximum effects at 100 nmol/L. ICA also increased optical absorbance value and EdU incorporation into nuclei of NSCs. ICA had no significant effects on the percentage of TuJ1 or GFAP-positive cells, and TuJ1 or GFAP protein expression in NSCs cultured in differentiation protocol. A total of 478 genes were found to be differentially regulated. Among signaling pathways significantly enriched by DEGs, mitogen activated protein kinase (MAPK) pathway was of interest. Blockade of extracellular signal-regulated kinase (ERK)/MAPK, other than p38/MAPK subfamily pathway partially abolished effects of ICA on neurosphere formation and EdU incorporation of NSCs. CONCLUSION: ICA can promote the selfrenewal of NSCs at least partially through ERK/MAPK signaling pathway.

Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray.

Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia L., on NSC behaviors and the underlying mechanisms. The self-renewal and proliferation of NSC were examined. We detected neuron- and/or astrocyte-specific markers using immunofluorescence and Western blotting, which could evaluate NSC differentiation. Psoralen treatment significantly inhibited neurosphere formation in a dose-dependent manner. Psoralen treatment increased the expression of the astrocyte-specific marker but decreased neuron-specific marker expression. These results suggested that Psoralen was a differentiation inducer in astrocyte. Differential gene expression following Psoralen treatment was screened using DNA microarray and confirmed by quantitative real-time PCR. Our microarray study demonstrated that Psoralen could effectively regulate the specific gene expression profile of NSC. The genes involved in the classification of cellular differentiation, proliferation, and metabolism, the transcription factors belonging to Ets family, and the hedgehog pathway may be closely related to the regulation.

[Immunoregulatory mechanisms of an optimal Chinese herbal monomer compound in mice with allergic rhinitis].

OBJECTIVE: To study the immunoregulatory effect of an optimal Chinese herbal monomer compound, which consists of three monomers, namely, icariin, baicalin and Astragalus saponin I, in a mouse model of allergic rhinitis. METHODS: A mouse model of allergic rhinitis was established by intraperitoneal injection of ovalbumin and aluminum hydroxide gel suspension. The splenic lymphocytes of the mice were separated, cultured in 96-well plates and divided into three groups: control group, concanavalin A group and compound group. Splenic lymphocyte proliferation was detected by cell counting kit-8 method at different time points. Cell cycle distribution was observed by flow cytometry (FCM) also at different time points. The changes of intracellular calcium concentration of splenic lymphocytes were measured by fluorescence microplate reader after the cells were incubated with fluorescence probe Fluo-3/AM. RESULTS: The Chinese herbal monomer compound could inhibit cell proliferation induced by concanavalin A (P<0.01). And the inhibition presented a time-effect relationship. With extending of the action time, the inhibition rate gradually increased and reached peak at the 48th hour. FCM test revealed the fact that concanavalin A could promote cells to enter into the mitosis by reducing the percentage of cells in G0/G1 phases while increasing the percentage of cells in S and G(2)/M phases. Compared with the concanavalin A, the compound could increase the percentage of cells in G(0)/G(1) phases and at the same time reduce the percentage of cells in S and G(2)/M phases at different time points, with the effect most significant at the 24th hour (P<0.05 or P<0.01). The results of the test taken by the fluorescence microplate reader revealed that the fluorescence value of the concanavalin A group increased with time in the previous 24 h while the compound could reduce this trend obviously, thus reduce the intracellular calcium concentration (P<0.01). CONCLUSION: The Chinese herbal monomer compound can inhibit the proliferation of cultured splenic lymphocytes of mice with allergic rhinitis. The effects of the compound of lowering intracellular calcium concentration and arresting cell cycle at G(0)/G(1) phases from entering into S and G(2)/M phases are responsible for its antiproliferation activity.

[Optimal combination of baicalin, icariin and Astragalus saponin I from a Chinese herbal compound Biminne].

OBJECTIVE: To study the optimal combined ratio of baicalin, icariin and Astragalus saponin I from a Chinese herbal compound Biminne. METHODS: Firstly, a mouse model of allergic rhinitis was established by intraperitoneal injection of ovalbumin (OVA) and aluminum hydroxide gel suspension, and the effective dose range of baicalin, icariin and Astragalus saponin I was detected by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt method. Secondly, 10 groups of combinations of baicalin, icariin and Astragalus saponin I assembled by U(10)(10(8)) form were employed to determine the optimal combination by means of analyzing of the inhibitory effect on the splenocyte proliferation. Finally, the effects of each effective ingredient and the optimal combination were compared by observing the splenocyte proliferation, the contents of interleukin-4 (IL-4), IL-5, interferon-gamma (IFN-gamma) in supernatant of the splenocyte cultures and the ratio of IL-4 to IFN-gamma in order to verify the result. RESULTS: Baicalin or icariin at concentrations ranging from 2 to 10 micromol/L, and Astragalus saponin I from 1 to 10 micromol/L effectively suppressed the splenocyte proliferation. When the proportion of baicalin, icariin and Astragalus saponin I was 1:2.14:2.65, the inhibitory effect was most remarkable. Further research confirmed the rationality of the optimal combination. CONCLUSION: An optimal combination of the major effective ingredients from Chinese herbal compound Biminne most effectively suppresses the proliferation of splenocytes from sensitized mice and regulates the cytokine secreting.

Metabonomic characterization of aging and investigation on the anti-aging effects of total flavones of Epimedium.

A liquid chromatography coupled with mass spectrometry (LC/MS) based metabonomics approach was applied to characterize the aging of rats, and the anti-aging effect of total flavones of Epimedium (TFE), a traditional Chinese medicine, has also been investigated. Serum samples collected from 4, 10, 18 and 24 month-old rats and TFE-administered rats have been profiled by LC/MS. Thirty age-related endogenous metabolites were discovered by partial least squares (PLS) and Hotelling's T(2) control chart, among which 25 metabolites were structurally identified by MS(n) analysis and ten of them were further confirmed via authentic chemicals. All important age-related metabolites, such as unsaturated fatty acids, saturated fatty acids, nucleotides, carnosine, ergothioneine and amino acids, displayed age-related changes, and most of them were reset to a younger level after TFE administration. This study indicated that aging could be characterized by changes of lipid metabolisms and accumulation of free radicals. The anti-aging effects of TFE might due to the intervention on lipid metabolism and its property of anti-oxidation.

[Effect of Epimedium flavonoids in retarding aging of C. elegans].

OBJECTIVE: To investigate effect of Epimedium flavonoids (EF), positively controlled by caloric restriction (CR) method, in retarding aging of the model organism C. elegans, in order to establish a basis for studying its action mechanism. METHODS: Experiment for life-time analysis was conducted on animals grouped into the blank group, the CR group, and the high and low dose EF groups to observe their mean lifespan, maximum lifespan and age-dependent mortality. And the reproductive capacity test and acute heat-stress analysis were carried out in the blank group and the high dose EF group to observe the subalgebra and the mean survival time under acute heat-stress at 35 degrees C. RESULTS: As compared with the blank group, the mean lifespan in the two EF group and the maximum lifespan in the high dose EF group were higher, and the age-dependent mortality in the high dose EF group was lower significantly (P<0.05 or P<0.01); as compared with the CR group, the mean lifespan and maximum lifespan in the high dose EF group were higher (P<0.01); but no significant difference of the subalgebra between the blank group and the high dose EF group was shown (P>0.05). Compared with the blank group, the mean lifespan in the high dose EF group was significantly prolonged under acute heat-stress at 35 degrees C (P<0.01). CONCLUSION: EF can retard the aging of C. elegans without damage on the reproductive capacity, and significantly improve its capacity against acute heat-stress.

[Establishment of a quantitative mathematical model of Shen-deficiency syndrome based on whole-genome transcriptional profiles].

OBJECTIVE: To establish a quantitative mathematical model of Shen-deficiency syndrome of TCM by utilizing whole-genome transcriptional profiles. METHODS: The 4, 10, 18, 24 months old SD rats were used, 24-months aged rats intervened by Epimedium Flavonoids (EF) were adopted in the experiment. Rats' hypothalamus, pituitary, adrenal, lymphocytes, bone, liver, and kidney, and spleen were taken for determining whole-genome mRNA expression with gene chip, and a quantitative nerve network model was established by utilizing the gene expression profile of different aged rats, then the model was used to evaluate the effects of EF on Shen-deficiency syndrome. RESULTS: Totally 199 genes showing age-dependent characteristics were screened out from the 7 kinds of tissue, most of them were neuro-endocrine immune related genes. Evaluation based on the mathematical model showed the age of hypothalamus, pituitary, adrenal, liver, kidney, bone, and spleen in the 24-months rats after EF intervention was 12.64, 10.87, 8.10, 12.70, 11.93, 13.14, and 10.13 months, respectively. CONCLUSION: A quantitative mathematical model can be established based on the gene expression profile, it is suitable for estimating the efficacy of Shen-tonifying drugs. EF can make the gene expression of elder close to the young state, suggesting that EF has action in improving Shen-deficiency syndrome and delaying senescence.