A PARP14/TARG1-Regulated RACK1 MARylation Cycle Drives Stress Granule Dynamics in Ovarian Cancer Cells.

Mono(ADP-ribosyl)ation (MARylation), a post-translational modification (PTM) of proteins, is emerging as a critical regulator of ribosome function and translation. Herein, we demonstrate that RACK1, a member of the tryptophan-aspartate repeat (WD-repeat) family of proteins and an integral component of the ribosome, is MARylated by the mono(ADP-ribosyl) transferase (MART) PARP14 in ovarian cancer cells. We mapped and confirmed the sites of MARylation, which occur on three acidic residues within blades 4 and 5 of ß-propeller domain of RACK1, a chaperone that shuttles and anchors proteins where needed. Site-specific MARylation of RACK1 is required for stress granule formation and promotes the colocalization of RACK1 to stress granules with key components, such as G3BP1, eIF3η, and 40S ribosomal proteins. In parallel, we observed reduced translation of a subset of mRNAs, including those encoding key cancer regulators (e.g., AKT). Treatment with a PARP14 inhibitor or mutation of the sites of MARylation on RACK1 blocks these outcomes. To re-set the system after prolonged stress and recovery, the ADP-ribosyl hydrolase TARG1 deMARylates RACK1 to dissociate the stress granules and return RACK1 and the 40S ribosomal subunit to the cytoplasm, allowing for a restoration of translation. Collectively, our results highlight the discovery of a PARP14/TARG1-regulated RACK1 MARylation cycle that controls stress granule assembly and disassembly in ovarian cancer cells.

Bone Protective Effects of Danggui Buxue Tang Alone and in Combination With Tamoxifen or Raloxifene in vivo and in vitro.

Danggui Buxue Tang (DBT), a traditional Chinese Medicine decoction containing Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), is commonly prescribed for women in China as a remedy for menopausal symptoms. Previous study indicated that DBT stimulated cell growth and differentiation of human osteosarcoma MG-63 cells and exhibited estrogenic properties via estrogen receptors (ERs). The present study aimed to study the bone protective effects of DBT and its potential interactions with selective estrogen receptor modulators (SERMs, tamoxifen and raloxifene) in both in vivo and in vitro models as they act via similar ERs. Six-month-old Sprague-Dawley rats were randomly assigned to the following treatments for 12 weeks: (1) sham-operated control group with vehicle (sham), (2) ovariectomized group with vehicle (OVX), (3) OVX with 17ß-estradiol (E2, 2.0 mg/kg day), (4) OVX with tamoxifen (Tamo, 1.0 mg/kg day), (5) OVX with raloxifene (Ralo, 3.0 mg/kg day), (6) OVX with DBT (DBT, 3.0 g/kg day), (7) OVX with DBT+Tamoxifen (DBT+Tamo), and (8) OVX with DBT+Raloxifene (DBT+Ralo). Effects of DBT and potential interactions between DBT and SERMs were also evaluated in MG-63 cells. DBT, tamoxifen, raloxifene, and their combinations significantly increased bone mineral density (BMD) and improved trabecular bone properties, including bone surface (BS), trabecular bone number (Tb.N), and trabecular bone separation (Tb.Sp), as well as restored changes in bone turnover biomarkers and mRNA expression of genes involved in bone metabolism in OVX rats. Furthermore, DBT, SERMs, and their combinations significantly increased serum estradiol and suppressed follicle stimulating hormone and luteinizing hormone in OVX rats, suggesting the possible involvement of the hypothalamus-pituitary-gonadal axis in mediating their bone protective effects. However, SERMs, but not DBT, significantly increased uterus index in OVX rats. DBT significantly induced ALP activity and estrogen response element-dependent transcription in MG-63 cells. Our study demonstrated that DBT alone and in combinations with SERMs could exert bone protective effects in vitro and in vivo.

Evaluation of the Pharmaceutical Properties and Value of Astragali Radix.

Astragali Radix (AR), a Chinese materia medica (CMM) known as Huangqi, is an important medicine prescribed in herbal composite formulae (Fufang) by Traditional Chinese medicine (TCM) practitioners for thousands of years. According to the literature, AR is suggested for patients suffering from “Qi”- and “Blood”-deficiencies, and its clinical effects are reported to be related to anti-cancer cell proliferation, anti-oxidation, relief of complications in cardiovascular diseases, etc. The underlying cell signaling pathways involved in the regulation of these various diseases are presented here to support the mechanisms of action of AR. There are two botanical sources recorded in China Pharmacopoeia (CP, 2015): Astragalus membranaceus (Fisch.) Bge. Var. mongohlicus, (Bge.) Hsiao, and Astragalus membranaceus (Fisch.) Bge. (Fam. Leguminosae), whose extracts of dried roots are processed via homogenization-assisted negative pressure cavitation extraction. Geographic factors and extraction methods have impacts on the pharmaceutical and chemical profiles of AR. Therefore, the levels of the major bioactive constituents of AR, including polysaccharides, saponins, and flavonoids, may not be consistent in different batches of extract, and the pharmaceutical efficacy of these bioactive ingredients may vary depending on the source. Therefore, the present review mainly focuses on the consistency of the available sources of AR and extracts and on the investigation of the biological functions and mechanisms of action of AR and of its major bioactive constituents. Furthermore, it will also include a discussion of the most popular AR composite formulae to further elucidate their chemical and biological profiles and understand the pharmaceutical value of AR.

A Chinese herbal decoction, Jian-Pi-Yi-Shen, regulates the expressions of erythropoietin and pro-inflammatory cytokines in cultured cells.

BACKGROUND: A Chinese herbal formula, namely Jian-Pi-Yi-Shen (JPYS), has been clinically prescribed for patients with chronic kidney disease associated-anemia, and which can improve the patient's immunological system. However, the mechanisms of JPYS involved in anemia and immune response have not been investigated. To study the role of JPYS in regulating hematopoietic and immunological functions, we investigated its activities on the expressions of erythropoietin and pro-inflammatory cytokines in cultured cells. METHODS: The standardized herbal extracts of JPYS (0-30 µg/ml) were applied onto cultured cells for 24-48 h. Total RNA was collected from the treated cells and subjected to real-time quantitative PCR analysis. Cultured HEK293T cells, transfected with a construct composed of hypoxia response element tagged with a luciferase gene, i.e. pHRE-Luc, were treated with JPYS extracts (1-30 µg/ml) for 24 h. The cell lysates were subjected to luciferase assay. RESULTS: The treatment with JPYS extract onto cultured HEK293T cells induced erythropoietin expression in a dose-dependent manner, having the highest response by ~ 50% of increase. In parallel, application of JPYS extract for 24 h stimulated expressions of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in cultured RAW 264.7 macrophages. In contrast, the pretreatment with JPYS extract suppressed expressions of IL-1ß, IL-6, and TNF-α in lipopolysaccharide-induced macrophages. CONCLUSIONS: These results confirmed the hematopoietic function of JPYS in regulating erythropoietin expression, as well as the bidirectional immune-modulatory roles of JPYS by regulating the expression of pro-inflammatory cytokines in cultures.

Quercetin Potentiates the NGF-Induced Effects in Cultured PC 12 Cells: Identification by HerboChips Showing a Binding with NGF.

Dementia is a persistent disorder of the mental processes and is strongly related to depression. However, the performance of current antidepression medicine is far from satisfactory. Herbal extract provides an excellent source to identify compounds for possible drug development against depression. Here, HerboChips were employed to search herbal compounds that could bind nerve growth factor (NGF). By screening over 500 types of herbal extracts, the water extract of Ginkgo Folium, the leaf of Ginkgo biloba, showed a strong binding to NGF. The herbal fractions showing NGF binding were further isolated and enriched. By using LC-MS/MS analysis, one of the NGF binding fractions was enriched, which was further identified as quercetin, a major flavonoid in Ginkgo Folium. Quercetin, similar to Ginkgo Folium extract, could enhance the effect of NGF in cultured PC 12 cells, including potentiation of neurite outgrowth and phosphorylation of Erk-1/2. This is the first report of discovering an NGF binding compound by using HerboChips from herbal extracts, which could be further developed for antidepression application.

Anisotropic, lightweight, strong, and super thermally insulating nanowood with naturally aligned nanocellulose.

There has been a growing interest in thermal management materials due to the prevailing energy challenges and unfulfilled needs for thermal insulation applications. We demonstrate the exceptional thermal management capabilities of a large-scale, hierarchal alignment of cellulose nanofibrils directly fabricated from wood, hereafter referred to as nanowood. Nanowood exhibits anisotropic thermal properties with an extremely low thermal conductivity of 0.03 W/m·K in the transverse direction (perpendicular to the nanofibrils) and approximately two times higher thermal conductivity of 0.06 W/m·K in the axial direction due to the hierarchically aligned nanofibrils within the highly porous backbone. The anisotropy of the thermal conductivity enables efficient thermal dissipation along the axial direction, thereby preventing local overheating on the illuminated side while yielding improved thermal insulation along the backside that cannot be obtained with isotropic thermal insulators. The nanowood also shows a low emissivity of <5% over the solar spectrum with the ability to effectively reflect solar thermal energy. Moreover, the nanowood is lightweight yet strong, owing to the effective bonding between the aligned cellulose nanofibrils with a high compressive strength of 13 MPa in the axial direction and 20 MPa in the transverse direction at 75% strain, which exceeds other thermal insulation materials, such as silica and polymer aerogels, Styrofoam, and wool. The excellent thermal management, abundance, biodegradability, high mechanical strength, low mass density, and manufacturing scalability of the nanowood make this material highly attractive for practical thermal insulation applications.

Calycosin Orchestrates Osteogenesis of Danggui Buxue Tang in Cultured Osteoblasts: Evaluating the Mechanism of Action by Omics and Chemical Knock-out Methodologies.

Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction commonly used to mitigate menopausal osteoporosis, contains two herbs: Astragali Radix (AR) and Angelicae Sinensis Radix (ASR). The exact efficacy of individual chemical(s) within DBT, or in any herbal mixture, is hard to be revealed. Calycosin and ferulic acid have been reported to be the predominant chemicals found within DBT, and its roles in regulating osteoblastic differentiation have been proposed here. To probe the roles of calycosin and ferulic acid, these chemicals were specifically depleted from the DBT extracts. Here, calycosin-depleted DBT (DBTΔcal) and ferulic acid-depleted DBT (DBTΔfa), generated by semi-preparative HPLC, were coupled with RNA-seq and metabolomics analyses to reveal the synergistic functions of individual chemicals within a complex herbal mixture. The expressions of osteogenic differentiation markers were significantly increased under the treatments of DBT and DBTΔfa. The DBT-induced genes were markedly reduced in the absent of calycosin, i.e., DBTΔcal. In cultured osteoblasts, the DBT-activated Wnt/ß-catenin and MAPK/Erk and signaling pathways were greatly affected when calycosin was depleted. By metabolomics analysis in DBT-treated osteoblasts, the profile of metabolites triggered by DBTΔcal showed distinction to that of DBT and/or DBTΔfa. Thus, our findings indicated that calycosin, rather than ferulic acid, could be an indispensable chemical in DBT to orchestrate multi-components of DBT in achieving maximal osteogenic properties.

Processing bulk natural wood into a high-performance structural material.

Synthetic structural materials with exceptional mechanical performance suffer from either large weight and adverse environmental impact (for example, steels and alloys) or complex manufacturing processes and thus high cost (for example, polymer-based and biomimetic composites). Natural wood is a low-cost and abundant material and has been used for millennia as a structural material for building and furniture construction. However, the mechanical performance of natural wood (its strength and toughness) is unsatisfactory for many advanced engineering structures and applications. Pre-treatment with steam, heat, ammonia or cold rolling followed by densification has led to the enhanced mechanical performance of natural wood. However, the existing methods result in incomplete densification and lack dimensional stability, particularly in response to humid environments, and wood treated in these ways can expand and weaken. Here we report a simple and effective strategy to transform bulk natural wood directly into a high-performance structural material with a more than tenfold increase in strength, toughness and ballistic resistance and with greater dimensional stability. Our two-step process involves the partial removal of lignin and hemicellulose from the natural wood via a boiling process in an aqueous mixture of NaOH and Na2SO3 followed by hot-pressing, leading to the total collapse of cell walls and the complete densification of the natural wood with highly aligned cellulose nanofibres. This strategy is shown to be universally effective for various species of wood. Our processed wood has a specific strength higher than that of most structural metals and alloys, making it a low-cost, high-performance, lightweight alternative.

Jasmonate-Elicited Stress Induces Metabolic Change in the Leaves of Leucaena leucocephala.

The plant Leucaena leucocephala was exposed to four jasmonate elicitors, i.e., jasmonic acid (JA), methyl jasmonic acid (MeJA), jasmonoyl-l-isoleucine (JA-Ile) and 6-ethyl indanoyl glycine conjugate (2-[(6-ethyl-1-oxo-indane-4-carbonyl)-amino]-acetic acid methyl ester) (CGM). The treatment was to mimic the herbivores and wounding stresses. By using NMR spectroscopy along with chemometric analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), the changes of metabolites in the leaves of L. leucocephala were determined under the stress as induced by the four elicitors. The challenge of JA-Ile caused an accumulation of lactic acid (6), ß-glucose (10), alanine (12), threonine (13), steroids (18), 3,4-dihydroxypyridine (19) and an unidentified compound 20. The chemometric analysis of the PCA and PLS-DA models indicated that the alternation of metabolites triggered by JA, MeJA, and CGM treatments were very minimum. In contrast, the treatment by JA-Ile could induce the most significant metabolic changes in the leaves. Moreover, there was very minimal new metabolite being detected in responding to the jasmonate-induced stresses. The results showed some metabolite concentrations changed after application of the elicitors, which may be related to a high level of tolerance to stress conditions as well as the strong ecological suitability of L. leucocephala.

Highly Compressible, Anisotropic Aerogel with Aligned Cellulose Nanofibers.

Aerogels can be used in a broad range of applications such as bioscaffolds, energy storage devices, sensors, pollutant treatment, and thermal insulating materials due to their excellent properties including large surface area, low density, low thermal conductivity, and high porosity. Here we report a facile and effective top-down approach to fabricate an anisotropic wood aerogel directly from natural wood by a simple chemical treatment. The wood aerogel has a layered structure with anisotropic structural properties due to the destruction of cell walls by the removal of lignin and hemicellulose. The layered structure results in the anisotropic wood aerogel having good mechanical compressibility and fragility resistance, demonstrated by a high reversible compression of 60% and stress retention of ∼90% after 10 000 compression cycles. Moreover, the anisotropic structure of the wood aerogel with curved layers stacking layer-by-layer and aligned cellulose nanofibers inside each individual layer enables the wood aerogel to have an anisotropic thermal conductivity with an anisotropy factor of ∼4.3. An extremely low thermal conductivity of 0.028 W/m·K perpendicular to the cellulose alignment direction and a thermal conductivity of 0.12 W/m·K along the cellulose alignment direction can be achieved. The thermal conductivity is not only much lower than that of the natural wood material (by ∼3.6 times) but also lower than most of the commercial thermal insulation materials. The top-down approach is low-cost, scalable, simple, yet effective, representing a promising direction for the fabrication of high-quality aerogel materials.

Wood-Based Nanotechnologies toward Sustainability.

With over 30% global land coverage, the forest is one of nature's most generous gifts to human beings, providing shelters and materials for all living beings. Apart from being sustainable, renewable, and biodegradable, wood and its derivative materials are also extremely fascinating from a materials aspect, with numerous advantages including porous and hierarchical structure, excellent mechanical performance, and versatile chemistry. Here, strategies for designing novel wood-based materials via advanced nanotechnologies are summarized, including both the controllable bottom-up assembly from the highly crystalline nanocellulose building block and the more efficient top-down approaches directly from wood. Beyond material design, recent advances regarding the sustainable applications of these novel wood-based materials are also presented, focusing on areas that are traditionally dominated by man-made nonrenewable materials such as plastic, glass, and metals, as well as more advanced applications in the areas of energy storage, wastewater treatment and solar-steam-assisted desalination. With all recent progress pertaining to materials' design and sustainable applications presented, a vision for the future engineering of wood-based materials to promote continuous and healthy progress toward true sustainability is outlined.

Tree-Inspired Design for High-Efficiency Water Extraction.

The solar steam process, akin to the natural water cycle, is considered to be an attractive approach to address water scarcity issues globally. However, water extraction from groundwater, for example, has not been demonstrated using these existing technologies. Additionally, there are major unaddressed challenges in extracting potable water from seawater including salt accumulation and long-term evaporation stability, which warrant further investigation. Herein, a high-performance solar steam device composed entirely of natural wood is reported. The pristine, natural wood is cut along the transverse direction and the top surface is carbonized to create a unique bilayer structure. This tree-inspired design offers distinct advantages for water extraction, including rapid water transport and evaporation in the mesoporous wood, high light absorption (≈99%) within the surface carbonized open wood channels, a low thermal conductivity to avoid thermal loss, and cost effectiveness. The device also exhibits long-term stability in seawater without salt accumulation as well as high performance for underground water extraction. The tree-inspired design offers an inexpensive and scalable solar energy harvesting and steam generation technology that can provide clean water globally, especially for rural or remote areas where water is not only scarce but also limited by water extraction materials and methods.

Chemical Differentiation of Dendrobium officinale and Dendrobium devonianum by Using HPLC Fingerprints, HPLC-ESI-MS, and HPTLC Analyses.

The stems of Dendrobium officinale Kimura et Migo (Dendrobii Officinalis Caulis) have a high medicinal value as a traditional Chinese medicine (TCM). Because of the limited supply, D. officinale is a high priced TCM, and therefore adulterants are commonly found in the herbal market. The dried stems of a closely related Dendrobium species, Dendrobium devonianum Paxt., are commonly used as the substitute; however, there is no effective method to distinguish the two Dendrobium species. Here, a high performance liquid chromatography (HPLC) method was successfully developed and applied to differentiate D. officinale and D. devonianum by comparing the chromatograms according to the characteristic peaks. A HPLC coupled with electrospray ionization multistage mass spectrometry (HPLC-ESI-MS) method was further applied for structural elucidation of 15 flavonoids, 5 phenolic acids, and 1 lignan in D. officinale. Among these flavonoids, 4 flavonoid C-glycosides were firstly reported in D. officinale, and violanthin and isoviolanthin were identified to be specific for D. officinale compared with D. devonianum. Then, two representative components were used as chemical markers. A rapid and reliable high performance thin layer chromatography (HPTLC) method was applied in distinguishing D. officinale from D. devonianum. The results of this work have demonstrated that these developed analytical methods can be used to discriminate D. officinale and D. devonianum effectively and conveniently.

Danggui Buxue Tang, a simple Chinese formula containing Astragali Radix and Angelicae Sinensis Radix, stimulates the expressions of neurotrophic factors in cultured SH-SY5Y cells.

BACKGROUND: Danggui Buxue Tang (DBT), a phytoestrogen-enriched Chinese herbal formula, serves as dietary supplement in stimulating the "Blood" functions of menopausal women. In traditional Chinese medicine (TCM) theory, "Blood" has a strong relationship with brain activities. Previous studies supported that some ingredients of DBT possessed neuronal beneficial functions. Therefore, the neurotrophic function and the mechanistic action of DBT were systematically evaluated in cultured human neuroblastoma SH-SY5Y cells. METHODS: The DBT-triggered protein expressions were analyzed by western blotting, while the transcriptional activities of promoters coding for related genes were revealed by luciferase assays. For mechanistic analysis of DBT, Erk1/2 and its inhibitor U0126 were analyzed. RESULTS: The application of DBT in cultured neuroblastoma cells showed the efficacies in: (1) up-regulation of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF); (2) activation of transcriptional activities of promoters coding for NGF, BDNF, GDNF; (3) activation of Erk1/2 and CREB; and (4) attenuation of the neurotrophic factor expression by the treatment of an Erk1/2 inhibitor. CONCLUSIONS: Our study supports that MAPK/Erk pathway acts as fundamental role in monitoring DBT-induced expression of neurotrophic factors in cultured human neuroblastoma cell. These results shed light in developing the working mechanism of this ancient herbal decoction for its neuronal function.

Highly Flexible and Efficient Solar Steam Generation Device.

Solar steam generation with subsequent steam recondensation has been regarded as one of the most promising techniques to utilize the abundant solar energy and sea water or other unpurified water through water purification, desalination, and distillation. Although tremendous efforts have been dedicated to developing high-efficiency solar steam generation devices, challenges remain in terms of the relatively low efficiency, complicated fabrications, high cost, and inability to scale up. Here, inspired by the water transpiration behavior of trees, the use of carbon nanotube (CNT)-modified flexible wood membrane (F-Wood/CNTs) is demonstrated as a flexible, portable, recyclable, and efficient solar steam generation device for low-cost and scalable solar steam generation applications. Benefitting from the unique structural merits of the F-Wood/CNTs membrane-a black CNT-coated hair-like surface with excellent light absorbability, wood matrix with low thermal conductivity, hierarchical micro- and nanochannels for water pumping and escaping, solar steam generation device based on the F-Wood/CNTs membrane demonstrates a high efficiency of 81% at 10 kW cm-2 , representing one of the highest values ever-reported. The nature-inspired design concept in this study is straightforward and easily scalable, representing one of the most promising solutions for renewable and portable solar energy generation and other related phase-change applications.

Superflexible Wood.

Flexible porous membranes have attracted increasing scientific interest due to their wide applications in flexible electronics, energy storage devices, sensors, and bioscaffolds. Here, inspired by nature, we develop a facile and scalable top-down approach for fabricating a superflexible, biocompatible, biodegradable three-dimensional (3D) porous membrane directly from natural wood (coded as flexible wood membrane) via a one-step chemical treatment. The superflexibility is attributed to both physical and chemical changes of the natural wood, particularly formation of the wavy structure formed by simple delignification induced by partial removal of lignin/hemicellulose. The flexible wood membrane, which inherits its unique 3D porous structure with aligned cellulose nanofibers, biodegradability, and biocompatibility from natural wood, combined with the superflexibility imparted by a simple chemical treatment, holds great potential for a range of applications. As an example, we demonstrate the application of the flexible, breathable wood membrane as a 3D bioscaffold for cell growth.

Mesoporous, Three-Dimensional Wood Membrane Decorated with Nanoparticles for Highly Efficient Water Treatment.

Wood, an earth-abundant material, is widely used in our everyday life. With its mesoporous structure, natural wood is comprised of numerous long, partially aligned channels (lumens) as well as nanochannels that stretch along its growth direction. This wood mesostructure is suitable for a range of emerging applications, especially as a membrane/separation material. Here, we report a mesoporous, three-dimensional (3D) wood membrane decorated with palladium nanoparticles (Pd NPs/wood membrane) for efficient wastewater treatment. The 3D Pd NPs/wood membrane possesses the following advantages: (1) the uniformly distributed lignin within the wood mesostructure can effectively reduce Pd(II) ions to Pd NPs; (2) cellulose, with its abundant hydroxyl groups, can immobilize Pd NPs; (3) the partially aligned mesoporous wood channels as well as their inner ingenious microstructures increase the likelihood of wastewater contacting Pd NPs decorating the wood surface; (4) the long, Pd NP-decorated channels facilitate bulk treatment as water flows through the entire mesoporous wood membrane. As a proof of concept, we demonstrated the use and efficiency of a Pd NPs/wood membrane to remove methylene blue (MB, C16H18N3ClS) from a flowing aqueous solution. The turnover frequency of the Pd NPs/wood membrane, ∼2.02 molMB·molPd-1·min-1, is much higher than the values reported in the literature. The water treatment rate of the 3D Pd NPs/wood membrane can reach 1 × 105 L·m-2·h-1 with a high MB removal efficiency (>99.8%). The 3D mesoporous wood membrane with partially aligned channels exhibits promising results for wastewater treatment and is applicable for an even wider range of separation applications.

A novel combination of four flavonoids derived from Astragali Radix relieves the symptoms of cyclophosphamide-induced anemic rats.

By using a feedback system control scheme, the best combination of formononetin, ononin, calycosin, and calycosin-7-O-ß-d-glucoside derived from Astragali Radix was shown to activate a hypoxia response element, a regulator for erythropoietin (EPO) transcription, in kidney fibroblast. In cyclophosphamide-induced anemic rats, the treatment of combined flavonoids, or EPO, improved the levels of red blood cells, white blood cells, hemoglobin, and hematocrit. In addition, the altered levels of antioxidant capacity, super oxidase dismutase, and malondialdehyde, triggered in anemic rats, were restored to control levels by the treatment of flavonoids. Here, we proposed a possible therapy by using the common flavonoids in treating anemia.

Danggui Buxue Tang (Astragali Radix and Angelicae Sinensis Radix) for menopausal symptoms: A review.

BACKGROUND: Traditional Chinese medicine (TCM) has contributed greatly to human health in past several thousand years. Today, the development of TCM is facing two obstacles: (i) quality control of herbal extract; and (ii) action mechanisms not known. OBJECTIVES: Among thousands of complex TCM formulations, Danggui Buxue Tang (DBT) is the simplest one. DBT is used to treat ailments in women and contains only two herbs, Astragali Radix (Huangqi; AR) and Angelicae Sinensis Radix (Danggui; ASR). The weight ratio of AR to ASR in DBT must be 5:1, as stipulated in AD 1247. By using DBT as a model formula, we develop a strategy to reveal the complexity of a traditional TCM formula. RESULTS: There are 3 levels of research directions: (i) the preparation of DBT and its rationale behind; (ii) the traditional theory of DBT is elucidated by chemical and biological determinations; and (iii) the action mechanisms of DBT are revealed. CONCLUSION: Through the chemical, biological, genomic and proteomic studies, a possible direction in resolving the preparation mythologies, pharmacological and mechanistic analyses of a TCM decoction is being proposed here.

A Modified Chinese Herbal Decoction (Kai-Xin-San) Promotes NGF-Induced Neuronal Differentiation in PC12 Cells via Up-Regulating Trk A Signaling.

Kai-Xin-San (KXS), a Chinese herbal decoction, has been applied to medical care of depression for thousands of years. It is composed of two functional paired-herbs: Ginseng Radix et Rhizoma (GR)-Polygalae Radix (PR) and Acori Tatarinowii Rhizoma (ATR)-Poria (PO). The compatibility of the paired-herbs has been frequently changed to meet the criteria of syndrome differentiation and treatment variation. Currently, a modified KXS (namely KXS2012) was prepared by optimizing the combinations of GR-PR and ATR-PO: the new herbal formula was shown to be very effective in animal studies. However, the cellular mechanism of KXS2012 against depression has not been fully investigated. Here, the study on KXS2012-induced neuronal differentiation in cultured PC12 cells was analyzed. In PC12 cultures, single application of KXS2012 showed no effect on the neuronal differentiation, but which showed robust effects in potentiating nerve growth factor (NGF)-induced neurite outgrowth and neurofilament expression. The potentiating effect of KXS2012 was mediated through NGF receptor, tropomyosin receptor kinase (Trk) A: because the receptor expression and activity was markedly up-regulated in the presence of KXS2012, and the potentiating effect was blocked by k252a, an inhibitor of Trk A. Our current results in cell cultures fully support the therapeutic efficacy of KXS2012 against depression.