ABSTRACT
Alzheimer's disease is a neurodegenerative disease that leads to dementia and poses a serious threat to the health of the elderly. Traditional Chinese medicine (TCM) presents as a promising novel therapeutic therapy for preventing and treating dementia. Studies have shown that natural products derived from kidney-tonifying herbs can effectively inhibit AD. Furthermore, endoplasmic reticulum (ER) stress is a critical factor in the pathology of AD. Regulation of ER stress is a crucial approach to prevent and treat AD. Thus, in this study, we first collected kidney-tonifying herbs, integrated chemical ingredients from multiple TCM databases, and constructed a comprehensive drug-target network. Subsequently, we employed the endophenotype network (network proximity) method to identify potential active ingredients in kidney-tonifying herbs that prevented AD via regulating ER stress. By combining the predicted outcomes, we discovered that 32 natural products could ameliorate AD pathology via regulating ER stress. After a comprehensive evaluation of the multi-network model and systematic pharmacological analyses, we further selected several promising compounds for in vitro testing in the APP-SH-SY5Y cell model. Experimental results showed that echinacoside and danthron were able to effectively reduce ER stress-mediated neuronal apoptosis by inhibiting the expression levels of BIP, p-PERK, ATF6, and CHOP in APP-SH-SY5Y cells. Overall, this study utilized the endophenotype network to preliminarily decipher the effective material basis and potential molecular mechanism of kidney-tonifying Chinese medicine for prevention and treatment of AD.
ABSTRACT
Osteoporosis (OP) is a systemic metabolic skeletal disorder characterized by a decline in bone mass, bone mineral density, and deterioration of bone microstructure. It is prevalent among the elderly, particularly postmenopausal women, and poses a substantial burden to patients and society due to the high incidence of fragility fractures. Kidney-tonifying Traditional Chinese medicine (TCM) has long been utilized for OP prevention and treatment. In contrast to conventional approaches such as hormone replacement therapy, TCM offers distinct advantages such as minimal side effects, low toxicity, excellent tolerability, and suitability for long-term administration. Extensive experimental evidence supports the efficacy of kidney-tonifying TCM, exemplified by formulations based on the renowned herb Cornus officinalis and its bioactive constituents, including morroniside, sweroside, flavonol kaempferol, Cornuside I, in OP treatment. In this review, we provide a comprehensive elucidation of the underlying pathological principles governing OP, with particular emphasis on bone marrow mesenchymal stem cells, the homeostasis of osteogenic and osteoclastic, and the regulation of vascular and immune systems, all of which critically influence bone homeostasis. Furthermore, the therapeutic mechanisms of Cornus officinalis-based TCM formulations and Cornus officinalis-derived active constituents are discussed. In conclusion, this review aims to enhance understanding of the pharmacological mechanisms responsible for the anti-OP effects of kidney-tonifying TCM, specifically focusing on Cornus officinalis, and seeks to explore more efficacious and safer treatment strategies for OP.
ABSTRACT
ObjectiveTo study the changes of mitochondrial function of ovarian granulosa cells in women of different ages and the effect of Erzhi-Tiangui prescription on in vitro fertilization-embryo transfer （IVF-ET） outcomes for elderly women， so as to verify the connotation of the "Seven-Seven" theory in the Huangdi's Internal Classic （《黄帝内经》）. MethodA total of 150 infertility patients undergoing IVF-ET at the Reproductive and Genetic Center of Integrative Medicine， Affiliated Hospital of Shandong University of Traditional Chinese Medicine were recruited and assigned into "hree-Seven/Four-Seven （30 cases）， Five-Seven （60 cases）， and Six-Seven （60 cases） groups according to the "Seven-Seven" theory. The Five-Seven and Six-Seven groups were further assigned into control and Chinese medicine subgroups using the random number plus envelope method， and the Chinese medicine group was administrated with Erzhi Tiangui prescription from the start day of controlled ovulation stimulation cycle to the trigger day. The IVF outcome was observed， and Western blot was employed to determine the levels of mitofusin 1 （MFN1）， mitofusin 2 （MFN2）， and dynamin-related protein 1 （Drp1） in the ovarian granulosa cells. ResultCompared with the Three-Seven/Four-Seven group， the control subgroups of the Five-Seven and Six-Seven groups showed decreased retrieved oocytes， two pronuclear （2PN） embryos， available embryos， high-quality embryos， clinical pregnancy rate， and live birth rate （P<0.05）. Moreover， the control subgroup of the Six-Seven group showed decreased fresh embryo transfer rate（P<0.05）. Compared with the control subgroup of the Five-Seven group， that of the Six-Seven group showed reduced retrieved oocytes， 2PN embryos， available embryos， high-quality embryos， and clinical pregnancy rate （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， 2PN oocytes， and available embryos than the control subgroup in the Five-Seven groups （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， than the control subgroup in the Six-Seven groups （P<0.05）. The control subgroup of the Six-Seven group showed lower expression levels of Mfn1 and Mfn2 and higher level of Drp1 than the control subgroup of the Five-Seven group （P<0.05）， which indicated that the levels of Mfn1 and Mfn2 in ovarian granulosa cells were down-regulated while the expression of Drp1 was up-regulated with aging （P<0.05）. The Chinese medicine subgroup had higher Mfn2 level and lower Drp1 level than the control subgroup in the Five-Seven group （P<0.05）， and the Chinese medicine subgroup had higher Mfn1 and Mfn2 levels and lower Drp1 level than then control subgroup in the Six-Seven group （P<0.05）. ConclusionsThe prognosis of IVF in women after "Five-Seven" became worse with aging， and the mitochondria in ovarian granulosa cells showed decreased fusion ability and increased fission， which verified the connotation of the "Seven-Seven" theory from the mitochondrial function. Erzhi Tiangui prescription can regulate the mitochondrial function of ovarian granulosa cells in elderly women， up-regulate the expression levels of Mfn1 and Mfn2 to promote mitochondrial fusion， and down-regulate the expression of Drp1 to reduce mitochondrial fission， thus alleviating the ovarian hypofunction caused by aging， improve the development potential of oocytes， and improve the IVF outcomes of elderly women. However， this prescription has limited efficacy for the elderly women in the age range of "Six-Seven".
ABSTRACT
Background: Kidney-tonifying herbs (KTHs) are widely used to treat unexplained recurrent spontaneous abortion (URSA) based on the theory of traditional Chinese medicine (TCM). However, there is still a lack of systematic evaluation and mechanistic explanation for these treatments. Objective: The purpose of this study was to assess the clinical efficacy, and to investigate the potential mechanisms, of KTH based on TCM for the treatment of URSA. Methods: A systematic literature search was conducted within PubMed, Embase, China Biomedical Literature database, Web of Science (WOS), China National Knowledge Infrastructure (CNKI) database, and the Wanfang database to find articles reporting on the Chinese herbal formula based around KTH for treating URSA, which were published between January 2010 and June 2021. A full bibliometric analysis was carried out; in addition, randomized controlled trial (RCT) articles were selected for systematic evaluation and meta-analysis. The drugs with the highest frequency of KTHs were screened for meta-analysis. Finally, network analysis and molecular docking were used to study the key components and potential pathway of KTHs in the treatment of URSA. Results: The meta-analysis included nine RCTs involving 1,054 subjects. Compared with the control groups, the clinical efficacy of TCM-based KTHs in the treatment of URSA patients significantly improved outcomes. Additionally, a component target pathway network was identified, which included 32 potential blood activating components and 113 main targets. Japonine, sopranol, lysine, and matrine were considered the most important bioactive molecules for KTHs. The key potential therapeutic pathway for URSA was a tumor-related signaling pathway. The target genes for URSA regulated by KTHs were highly similar to tumor biological processes such as the regulation of apoptotic signaling pathways, inflammatory responses, angiogenesis, and epithelial metabolic transition. Conclusion: KTH has great potential for treating URSA. Because the maintenance of pregnancy has a high similarity with tumor invasion, the research relating to tumor mechanisms should also be followed up as it may lead to new ideas and breakthroughs for research into URSA. At the same time, embryonic and decidual cells share a high degree of cellular heterogeneity and spatial structural complexity with tumor cells, and a single cell combined with spatial omics may be the best future approach for validating KTH mechanisms.
ABSTRACT
As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing-nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected.
Subject(s)
Medicine, Chinese Traditional , Regenerative Medicine , Stem Cells , Drugs, Chinese Herbal/pharmacology , Humans , Kidney/drug effectsABSTRACT
As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing-nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected.
Subject(s)
Humans , Drugs, Chinese Herbal , Pharmacology , Kidney , Medicine, Chinese Traditional , Regenerative Medicine , Stem CellsABSTRACT
Primary osteoporosis (POP) is one of the most common diseases in the elderly people resulting in high risk of fracture and poor quality of life. In addition to the pathological changes in bone mass, most of the POP patients also suffer from Chinese medicine (CM) syndromes of Shen (Kidney) essence deficiency. Shen essences are highly related to bone. Shen essence deficiency plays an important part in the development of POP and a better diagnosis of POP could be made by combining CM syndromes with Western medicine risk factors. Treatments of POP should aim at both increasing the bone mass and relieving the syndromes of Shen essence deficiency. Clinical study confirmed that treating POP patients with Shen-tonifying herbs could increase the bone mass and relieve the CM syndromes of POP patients. Basic researches clarified the mechanism by which Shen-tonifying herbs increased bone mass in animal models. The mechanisms by which Shentonifying herbs relieve the CM syndromes are still in investigation.
Subject(s)
Bone and Bones/pathology , Drugs, Chinese Herbal/therapeutic use , Kidney/pathology , Medicine, Chinese Traditional , Osteoporosis/drug therapy , Aging/pathology , Animals , Bone and Bones/physiopathology , HumansABSTRACT
Objective: To investigate the mechanisms through which kidney-tonifying herbs (KTHs) and liver-clearing herbs (LCHs) in Dingjing Decoction (DJD) regulate premature ovarian failure (POF). Methods: One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results: The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol (CORT) in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms. Gonadotropin-releasing hormone (GnRH), which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion: KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. GnRH is the key biological molecule associated with KTHs intervention.
ABSTRACT
Primary osteoporosis (POP) is one of the most common diseases in the elderly people resulting in high risk of fracture and poor quality of life. In addition to the pathological changes in bone mass, most of the POP patients also suffer from Chinese medicine (CM) syndromes of Shen (Kidney) essence deficiency. Shen essences are highly related to bone. Shen essence deficiency plays an important part in the development of POP and a better diagnosis of POP could be made by combining CM syndromes with Western medicine risk factors. Treatments of POP should aim at both increasing the bone mass and relieving the syndromes of Shen essence deficiency. Clinical study confirmed that treating POP patients with Shen-tonifying herbs could increase the bone mass and relieve the CM syndromes of POP patients. Basic researches clarified the mechanism by which Shen-tonifying herbs increased bone mass in animal models. The mechanisms by which Shentonifying herbs relieve the CM syndromes are still in investigation.
Subject(s)
Animals , Humans , Aging , Pathology , Bone and Bones , Pathology , Drugs, Chinese Herbal , Therapeutic Uses , Kidney , Pathology , Medicine, Chinese Traditional , Osteoporosis , Drug TherapyABSTRACT
Traditional Chinese herbal formulae Liu wei di huang (LW) (six-ingredient pill with Rehmannia) and Jin gui shen qi wan (JG) (kidney Qi pill from the golden cabinet) were analysed for Ca, Fe, Mg, Mn, Na, K and Zn at different decoction intervals by atomic absorption spectroscopy. LW and JG were used to improve the kidney function. JG was higher in all elements than LW. K (1691.29 - 2372.71 mg l(-1)) was highest in both formulae LW and JG followed by Ca (245.31 - 562.91 mg l(-1)). Ca, Fe, Mg, Mn and K were highest at 40 min for LW and Fe, Mn, Na and K were highest at 40 min for JG. Chemometrics such as principal component analysis, hierarchical cluster analysis and linear discriminate analysis were applied to classify the data and to understand the relation between the elements. Metal intake related to the consumption of decoction has also been studied. Mn made the highest contribution to average daily dietary intakes from the formulae.
