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ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription （JPTL） and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group， model group， JPTL low-， medium- and high-dose groups （5， 10， 20 g·kg-1） and positive drug （celecoxib， 0.03 g·kg-1） group， with 10 in each group （po，once a day）. Complete freund's adjuvant （CFA） was used to induce the model of chronic inflammatory pain， and xylene-induced ear swelling test， hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of prostaglandin E2 （PGE2）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum and inflammatory paw of mice with chronic inflammatory pain， and the expressions of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， cyclooxygenase 1 （COX1）， cyclooxygenase 2 （COX2） and mitogen-activated protein kinases （MAPKs） in inflammatory paw were detected by Western blot， to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group， there was a significant increase in the ear swelling of xylene-induced model mice， a shortened paw withdrawal latency in the hot plate test （P<0.01）. Compared with the model group， JPTL remarkably increased the inhibition rate of xylene-induced ear swelling （P<0.05， P<0.01）， prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing （P<0.05， P<0.01）. Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased， the threshold of mechanical pain was decreased and the threshold of cold pain was increased （P<0.05， P<0.01）， the protein contents of AQP1 and AQP3 in inflammatory feet were increased， and the contents of IL-1β， IL-6， TNF-α， PGE2 and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK， p-JNK and p-ERK in inflammatory feet were increased （P<0.01）. Compared with the model group， JPTL relieved paw swelling of mice with chronic inflammatory pain， elevated mechanical withdrawal threshold while decreased cold withdrawal threshold， with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration （P<0.05， P<0.01）. Moreover， JPTL down-regulated AQP1， AQP3， COX2， p-p38 MAPK， p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β， IL-6， TNF-α， and PGE2 in serum and/or inflammatory paw， but it had no significant effect on COX1 （P<0.05， P<0.01）. ConclusionJPTL has anti-swelling and analgesic effects， and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway， which provides an experimental basis for the clinical application of JPTL.
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OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).@*METHODS@#This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.@*RESULTS@#The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.@*CONCLUSIONS@#TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).
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Humans , Female , Breast Neoplasms/therapy , Acupuncture Points , Retrospective Studies , Lymphedema/complications , Acupuncture Therapy/adverse effects , Upper Extremity , Treatment OutcomeABSTRACT
ObjectiveTo assess the curative effects of Fangji Huangqi detumescence prescription （FHDP） on synovitis and polarization of synovial macrophages of knee osteoarthritis （KOA） model in rats induced by Hulth method. MethodThirty-six rats were randomly divided into sham operation group， model group， high-dose， medium-dose， and low-dose （29.16， 14.58， and 7.29 g·kg-1） FHDP groups， and loxoprofen sodium （16.2 mg·kg-1） group. KOA model in rats was induced by modified Hulth method. Six weeks after the operation， rats were given high， medium， and low concentrations of FHDP， normal saline （NS）， and loxoprofen sodium according to the group to intervene， and sacrificed after 2-week administration. Synovium and cartilage histopathological changes were observed after hematoxylin-eosin （HE） staining. Flow cytometry （FCM） and immunofluorescence （IF） test were used to evaluate the polarization of M1/M2 macrophages. Immunohistochemistry （IMC） and enzyme-linked immunosorbent assay （ELISA） were used to detect the related protein expression levels of macrophage polarization， such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and matrix metalloproteinase-13 （MMP-13） in joint tissues and serum. ResultCompared with the sham operation group， Krenn and Mankin scores in the model group were significantly increased （P<0.01）. Compared with the model group， Krenn score was decreased in all administration groups （P<0.05， P<0.01）， but there was no significant difference in Mankin score in any administration groups. Compared with the sham operation group， M1/mø （CD38+） ratio in the model group was significantly increased （P<0.01）， and M2/mø （CD206+） ratio in the model group was decreased （P<0.05）. Compared with the model group， M1/mø ratio in the high， medium， and low-dose FHDP groups was decreased （P<0.05， P<0.01）， but M2/mø ratio was increased in all administration groups （the difference had no statistical significance）. Compared with the sham operation group， M1/M2 ratio in the model group was significantly increased （P<0.01）. Compared with the model group， M1/M2 ratio in all FHDP groups was significantly decreased （P<0.01）， and M1/M2 ratio in the high and medium-dose FHDP groups was lower than that in the loxoprofen sodium group （P<0.05）. Compared with the sham operation group， the levels of TNF-α， IL-1β， and MMP-13 in synovium and cartilage of the model group were significantly increased （P<0.01）， the level of IL-10 was significantly decreased （P<0.01）. Compared with the model group， the levels of TNF-α and IL-1β in synovium were decreased in all administration groups （P<0.05）， but the difference of the levels of MMP-13 and IL-10 in synovium had no statistical significance. The level of inflammatory mediators in cartilage was not affected in all administration groups. Compared with the sham operation group， the levels of TNF-α and IL-β in serum of the model group were significantly increased （P<0.01）， the level of IL-10 was decreased （P<0.05）. Compared with the model group， the level of TNF-α in the high-dose FHDP group was decreased （P<0.05）， and the level of IL-10 was increased in all administration groups （P<0.05， P<0.01）. The difference of the level of IL-β in all administration groups had no statistical significance. ConclusionFHDP attenuated the synovitis of KOA rats. FHDP exert the effect on the releasing of proinflammatory cytokines and MMP by inhibiting the polarization of M1 macrophages in synovium， and had no significant effect on the polarization of M2 macrophages. Modulating the imbalanced polarization of synovial macrophages was a possible mechanism of FHDP on attenuating synovitis and treating KOA.
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Objective: To explore the network regulation mechanism of blood-activating and hemostatic and detumescent and analgesic traditional effects of Panax notoginseng. Methods: Targets of the 12 components of P. notoginseng absorbed in plasma were predicted according to the reverse pharmacophore method. Gene ontology (GO) function enrichment and pathway analysis of the targets were analyzed by Omicsbean online analysis software and String 10 database. Finally, Cytoscape software was used to construct the network pharmacology map. Results: A total of 12 compounds (notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rh1, ginsenoside Rg2, ginsenoside Rb1, ginsenoside Rd, ginsenoside F2, ginsenoside Rg3, ginsenoside Rk1, dencichine and quercetin) affected 65 pathways through 65 related targets, which were associated with anti-thrombosis, fibrinolysis, angiogenesis, vasodilation, blood coagulation, anti-inflammation and analgesia. The network of "compound-target-pathway-pharmacological action-efficacy" was also constructed. Conclusion: P. notoginseng interferes with multiple biological processes related to activating blood circulation, hemostasis, detumescence and analgesia by acting on several key proteins such as F2, F10, PLAT, VEGFA, NOS2, IL6, PTGES, OPRD1, etc.
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OBJECTIVE： To study the anti-inflammatory and detumescent pharmacodynamic material basis of Jingyaokang capsule， and to provide reference for secondary development， the establishment of quality control method and technological upgrading of the preparations. METHODS： The constituents of Jingyaokang capsule were extracted and separated with different solvents and macroporous adsorption resin to obtain constituent A （overall enrichment part）， constituent B （chloroform extraction part）， constituent C （water-course part） and constituent D （elution part of 60％ ethanol）. Using dexamethasone acetate as positive control， the anti-inflammatory and detumescent effects of Jingyaokang capsule and different extraction parts （constituents A， B， C， D） were investigated by mice ear edema and rat paw edema tests to screen the active fraction. UPLC-Q-TOF-MS method was used to analyze active constituent， identify compounds and attribute medicinal material. RESULTS： Anti-inflammatory and detumescent effects of constituent B （chloroform extraction part）+constituent D （elution part of 60％ ethanol） were similar to those of Jingyaokang capsule in rats or mice， indicating both had synergistic anti-inflammatory and detumescent effects and were active constituents of Jingyaokang capsule. UPLC-Q-TOF-MS detection and identification showed that constituent B contained 13 compounds as strychnine， phellodendrine， periplogenin， tetraketone alcohol， 11-carbonyl-β-mastic acid， attributing to Strychnos nux-vomica， Stephania tetrandra， Periploca sepium， Lycopodium japonicum， Boswellia carterii， etc. Constituent D contained 7 compounds as adenine， hydroxysafflower yellow A， phellodendrine， neoeriocitrin， zingibroside R1， attributing to rainworm， Carthamus tinctorius， Stephania tetrandra， Davallia mariesii， Achyranthes bidentata， etc. CONCLUSIONS： Jingyaokang capsule shows the significant anti-inflammation and detumescent effects. The chloroform extraction part is synergistic with 60％ ethanol elution part， which are the active constituents of anti-inflammation and detumescence，mainly including alkaloids， flavonoids and boswellic acids.