Magnolia Officinalis Research Articles

Gold nano particles synthesized from Magnolia officinalis and anticancer activity in A549 lung cancer cells

Nanotechnology is creating a bang in each and every field of life science. Scientists are mounting their interest of research towards gold nanoparticles as they are capable with bigger and advanced properties.Traditionally nanoparticles have been manufactured by various chemical and physical methods but have negative impact on the environment and are also highly toxic. Synthesis of nanoparticles by using plant extracts is substituting the conventional methods and it is eco-friendly too. In the current study, we prepared gold nanoparticles (AuNPs) from Magnolia officinalis, which is identified as an eco-friendly and less toxic method. Incorporation of AuNPs was renowned by UV-absorbance and it shows peak values. Nanoparticle sizes are recognized by dynamic light scattering scrutiny and it shows a value of 128 nm. Besides, high resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray analysis (EDX) and atomic force microscopy (AFM) incorrigibly define the shape of the AuNPs which are present in the complex materials. Fourier-transform infrared spectroscopy (FTIR) findings display that the active molecules are positioned in the plane of the AuNPs. Similarly, anticancer efficacy of AuNPs have been assessed in A549 cells. our study show that AuNPs effectively provoke cytotoxicity, and apoptosis by inflecting apoptotic gene expressions in A549 cells.

Effect of Macleaya cordata and Magnolia officinalis plant extracts on oxidative stress control in lambs fed a high-concentrate diet.

ObjectiveThe objective of this experiment was to compare conventional antioxidants and plant extracts for oxidative stress control in lambs fed a high-concentrate diet.MethodsForty-eight male Dorper×Santa Ines lambs with an initial weight of 20±1.49 kg and 60 days of age, were used to evaluate the effects of feeding a combination of Macleaya cordata and Magnolia officinalis plant extracts (0 vs 320 mg/kg dry matter [DM]) in combination with selenium+vitamin E (0 vs 100 IU/kg DM of vitamin E and 0.1 mg/kg DM of selenium) in a completely randomized block design in a 2×2 factorial arrangement. The animals were housed in individual pens and received a high-concentrate diet consisting of 80% whole corn and 20% protein pellet for 60 days. The animals were weighed at the beginning of the experiment and every 14 days for performance monitoring. Three blood samplings were performed during the experimental period for the evaluation of oxidative and protein parameters.ResultsThe treatments with vitamin E and selenium as additives had a positive influence on final weight, daily weight gain, carcass weight, and selenium content in longissimus muscle (p = 0.01). Plant extracts tended to improve final weight (p = 0.064) and daily weight gain (p = 0.059), showing similar effect as selenium and vitamin E. There was no effect of treatment on blood proteins, indicating that the animals were healthy throughout the experiment.ConclusionThe use of plant extracts had a similar effect as the addition of selenium and vitamin E, with dietary inclusion of additives resulting in better performance of lambs but both supplements did not have strong influence on oxidative stress.

Honokiol and Magnolol Inhibit Growth, Metastasis and Induce Apoptosis in Human Cholangiocarcinoma

Cholangiocarcinoma (CCA) is biliary tract malignancy. Because no specific biomarkers are available, CCA patients frequently present with disseminated tumour that is too late for curative treatment, leading to a high mortality rate. Honokiol and magnolol are the hydroxylated biphenyl compounds isolated from Magnolia officinalis. Many studies have reported that honokiol and magnolol have antitumour effects on various types of cancer, but the evidence of the effects of these compounds on CCA cells has not yet been reported. This study therefore aims to evaluate the antitumour activities of honokiol and magnolol on CCA cell lines. The CCA cell lines were incubated with honokiol and magnolol before determining their responses. The results indicate that low concentrations of honokiol and magnolol suppressed CCA proliferation by induction of cell cycle arrest at G0/G1 and down-regulation of cyclin D1 protein. Moreover, these compounds exhibited an antimetastasis ability mediated by inhibiting migration, adhesion, and the MMP activities of CCA cells. In addition, at high concentrations of honokiol and magnolol activated CCA cell death associated with the apoptosis signalling pathway, along either an intrinsic or extrinsic pathway. Our data provides evidence that honokiol and magnolol have potential anticancer properties and are promising compounds for alternative CCA treatment.

Honokiol inhibits breast cancer cell metastasis by blocking EMT through modulation of Snail/Slug protein translation

Honokiol (HNK), an active compound isolated from traditional Chinese medicine Magnolia officinalis, has shown potent anticancer activities. In the present study, we investigated the effects of HNK on breast cancer metastasis in vitro and in vivo, as well as the underlying molecular mechanisms. We showed that HNK (10-70 μmol/L) dose-dependently inhibited the viability of human mammary epithelial tumor cell lines MCF7, MDA-MB-231, and mouse mammary tumor cell line 4T1. In the transwell and scratch migration assays, HNK (10, 20, 30 μmol/L) dose-dependently suppressed the invasion and migration of the breast cancer cells. We demonstrated that HNK (10-50 μmol/L) dose-dependently upregulated the epithelial marker E-cadherin and downregulated the mesenchymal markers such as Snail, Slug, and vimentin at the protein level in breast cancer cells. Using a puromycin incorporation assay, we showed that HNK decreased the Snail translation efficiency in the breast cancer cells. In a mouse model of tumor metastasis, administration of HNK (50 mg/kgevery day, intraperitoneal (i.p.), 6 times per week for 30 days) significantly decreased the number of metastatic 4T1 cell-derived nodules and ameliorated the histological alterations in the lungs. In addition, HNK-treated mice showed decreased Snail expression and increased E-cadherin expression in metastatic nodules. In conclusion, HNK inhibits EMT in the breast cancer cells by downregulating Snail and Slug protein expression at the mRNA translation level. HNK has potential as an integrative medicine for combating breast cancer by targeting EMT.

Reynoutria Japonica from Traditional Chinese Medicine: A Source of Competitive Adenosine Deaminase Inhibitors for Anticancer.

Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents. In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors. Extracts from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by 1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin. Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.

Comparative Study on Dpph Free Radical Scavenging Activity of 25 Kinds of Traditional Chinese Medicinal Plants

Aims: To determine and compare the antioxidant activity of water and ethanol extract of 25 kinds of traditional chinese medicinal plants.
 Results: The ethanol extract of 4 kinds of medicinal herbs had the strongest scavenging activity. They were Magnolia officinalis, Rheum officinale, Psoralea corylifolia and Radix Bupleuri. In addtion, Rheum laciniatum, Chrysanthemum morifolium, Magnolia officinalis and Salvia miltiorrhiza had the strongest scavenging activity of their water extract. On the basis of the above comparison, we evaluated EC50 and total phenolic content of their ethanol extract. The EC50 of Magnolia officinalis, Rheum officinale, Psoralea corylifolia and Radix Bupleuri were 2.75mg·mL-1, 11.82mg·mL-1, 25.22mg·mL-1and 42.67mg·mL-1. The total phenlic content of them were 4.80μg·L-1 , 1.19μg·L-1, 1.07μg·L-1 and 0.75μg·L-1, respectively.
 Conclusion: The results showed the correlation between the antioxidant activity and the total phenol content. Furthermore, the reaction time of the DPPH test affected the free radical scavenging, which reflected the difference of the extract component would impact the test method.

Inhibition of Rat CYP1A2 and CYP2C11 by Honokiol, a Component of Traditional Chinese Medicine.

Honokiol, a major constituent isolated from Magnolia officinalis, is regarded as a phytochemical marker and bioactive substance present in many traditional Chinese medicines. However, the effect of honokiol on cytochrome P450 (CYP) has not been thoroughly investigated. The aim of this study was to investigate the effect of honokiol on CYP1A2 and CYP2C11 in vitro and in vivo. The effect of honokiol on CYP1A2 and CYP2C11 was investigated with rat liver microsomes (RLMs) by measuring phenacetin and tolbutamide metabolism (probe drugs for CYP1A2 and CYP2C11, respectively), and then explored in vivo by measuring the effect of honokiol (2.5 and 5mg/kg, intravenous injection) on the pharmacokinetics of theophylline and tolbutamide (probe drugs for CYP1A2 and CYP2C11, respectively) in rats in vivo. Honokiol inhibited the formation of acetaminophen from phenacetin and 4-hydroxytolbutamide from tolbutamide in RLMs, with inhibition constant (Ki) values of 1.6μM and 16.5μM, respectively. In vivo, honokiol (2.5 or 5.0mg/kg) increased the half-life (t1/2) of theophylline by 40.9% and 119.9%, decreased the clearance (CL) by 23.8% and 42.9%, and increased the area under the curve (AUC) by 41.3% and 83.4%, respectively. Similarly, the t1/2 of tolbutamide increased by 25.5% and 33.8%, the CL decreased by 14.3% and 19.1%, and the AUC increased by 19.2% and 25.7%, respectively. The inhibition of CYP1A2 by honokiol is greater than the inhibition of CYP2C11. The changes in the pharmacokinetics of theophylline and tolbutamide in rats treated with honokiol are due to the inhibition of CYP1A2 and CYP2C11 activity in a dose-dependent manner.

Antifungal Effect of Magnolol and Honokiol from Magnolia officinalis on Alternaria alternata Causing Tobacco Brown Spot.

In this study, two phenol compounds, magnolol and honokiol, were extracted from Magnolia officinalis and identified by LC-MS, 1H- and 13C-NMR. The magnolol and honokiol were shown to be effective against seven pathogenic fungi, including Alternaria alternata (Fr.) Keissl, Penicillium expansum (Link) Thom, Alternaria dauci f.sp. solani, Fusarium moniliforme J. Sheld, Fusarium oxysporum Schltdl., Valsa mali Miyabe & G. Yamada, and Rhizoctonia solani J.G. Kühn, with growth inhibition of more than 57%. We also investigated the mechanisms underlying the potential antifungal activity of magnolol and honokiol. The results showed that they inhibited the growth of A. alternata in a dose-dependent manner. Moreover, magnolol and honokiol treatment resulted in distorted mycelia and increased the cell membrane permeability of A. alternata, as determined by conductivity measurements. These results suggest that magnolol and honokiol are potential antifungal agents for application against plant fungal diseases.

Inhibition of human carboxylesterases by magnolol: Kinetic analyses and mechanism

Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.

Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.

A FLIPR Assay for Discovery of GABAA Receptor Modulators of Natural Origin.

A fluorometric imaging plate reader (FLIPR) assay utilizing Chinese hamster ovary (CHO) cells stably transfected with GABAA receptors of α 1 β 2 γ 2 subunit composition was evaluated and validated for rapid screening of plant extract libraries and efficient localization of active compounds in extracts. Validation was performed with pure compounds and extracts known to contain allosteric GABAA receptor modulators. Plants extracts that had been previously reported as active in an assay using Xenopus laevis oocytes transiently expressing GABAA receptors of α 1 β 2 γ 2 subunit composition were also active in the FLIPR assay. A protocol for HPLC-based activity profiling was developed, whereby separations of 0.4 - 1.2 mg of extracts on an analytical HPLC column were found to be sufficient for the sensitivity of the bioassay. The protocol successfully localized the activity of known GABAergic natural products, such as magnolol in Magnolia officinalis, valerenic acid in Valeriana officinalis, and piperine in Piper nigrum extract. EC50 values of compounds (magnolol: 4.81 ± 1.0 µM, valerenic acid: 12.56 ± 1.2 µM, and piperine: 5.76 ± 0.7 µM) were found to be comparable or lower than those reported using Xenopus oocyte assays.

Honokiol alleviates acetaminophen-induced hepatotoxicity via decreasing generation of acetaminophen-protein adducts in liver

AimAcetaminophen (APAP) overdose is the most frequent cause of drug-induced liver damage. Magnolia officinalis is a traditional hepatoprotective Chinese medicine and Honokiol (HO) is the major active constituent. The present study was to investigate the effect of HO on APAP-induced hepatotoxicity and related mechanisms. Main methodsFour groups of mice were subjected to treatment as vehicle, APAP, APAP + HO and APAP + HO + NRF2 inhibitor. The morphological and biochemical assessments were used to evaluate the hepatoprotective effects. The extent of APAP-protein adducts was determined through evaluate the hepatic content 3‑(cystein‑S‑yl)acetaminophen (APAP-Cys), the hydrolysis products of APAP-protein adducts. The activities of CYP2E1, CYP1A2 and CYP3A4 were evaluated by cocktail incubation, and the protein expression levels of NRF2, GCLC, GCLM, GS and GST were evaluated by western blot analysis. Key findingsMorphological and biochemical assessments clearly demonstrated that HO could alleviate APAP-induced liver damage. The hepatoprotective effect of HO was positively associated with the reduction of APAP-protein adducts. Further investigation suggested that HO induced inhibition of CYP 2E1 and CYP2A1 as well as upregulation of GSH co-contributed to the reduction of APAP-protein adducts. Furthermore, HO induced activations of NRF2 and its target enzymes, such as GCLC, GCLM and GST, gave rise to the upregulation of GSH. SignificanceOur results suggested that HO could alleviate APAP-induced liver damage through reducing the generation of APAP-protein adducts, which might be mediated by inhibiting the activity of CYP 2E1 and CYP2A1 as well as enhancing the generation of GSH via NRF2 pathway.

Dynamic Changes of Eight Bioactive Constituents in Magnoliae Officinalis Cortex Based on UFLC-QTRAP-MS/MS Combined with Grey Relational Analysis

Background: Magnoliae Officinalis Cortex is a well-known traditional Chinese herbal medicine with vast clinical consumption owing to its positive effects. However, little attention has been devoted to analyzing the dynamic changes of the chemical constituents of Magnoliae Officinalis Cortex in different growth periods. Methods: In this study, all analyses were performed on UFLC -20ADXR system and a SynergiTM Hydro-RP 100 Å column (100 mm×2.0 mm, 2.5µm). The mobile phase consisted of water containing 0.1% formic acid (A) and acetonitrile containing 0.1% formic acid (B). The target constituents, including two lignans, two alkaloids, two flavonoids, one phenylpropanoid glycoside, and one organic acid, were analyzed in both positive and negative ion modes with accurate and sensitive multiple reaction monitoring (MRM) mode. Results: The correlation coefficients of all the calibration curves were higher than 0.9992. Relative standard deviations of intra- and inter-day precisions of the eight analytes were all lower than 4.01% and the recoveries were in the range from 98.62% to 102.46%. Grey relational analysis was performed to evaluate the samples according to the contents of 8 constituents. The results showed that the quality of Magnoliae Officinalis Cortex collected at traditional harvest time was much better, and the higher the age, the better the quality. Conclusion: The proposed method is useful for the assessment on the quality of Magnoliae Officinalis Cortex, and this study provides the basis for exploring the quality forming mechanism of Magnoliae Officinalis Cortex medicinal materials and choosing the suitable harvesting period.

Role of Nrf2 in the antioxidation and oxidative stress induced developmental toxicity of honokiol in zebrafish

Honokiol, the main bioactive component of Magnolia officinalis, has a variety of pharmacological actions. However, its toxicity has rarely been reported. According to previous studies performed in our laboratory, honokiol microemulsion has embryo developmental toxicity. For further exploration, Zebrafish embryos were exposed to different doses of honokiol microemulsion to record the rates of mortality, malformation, and hatching. We found that high doses of honokiol microemulsion (0.6 and 0.9 μg/ml) increased mortality, inhibited hatching, caused malformation and reduced swimming activities. The low-dose group (0.15 and 0.30 μg/ml) had decreased production of reactive oxygen species (ROS), but the high-dose group had inhibited superoxide dismutase (SOD) enzyme activity and increased ROS content. The mRNA expression of sod1, sod2, catalase(cat), and heme oxygenase 1 (ho1) was up-regulated at low doses but down-regulated at high doses. The nuclear factor E2-related factor 2 (Nrf2) mRNA expression increased at low doses but decreased at high doses. After knocking down Nrf2 in zebrafish embryos, the rates of mortality and malformation were markedly increased and the hatching rate was significantly decreased. These results suggest that honokiol has antioxidative effects at low doses but causes embryo-developmental toxicity at high doses, and the Nrf2 gene may play a pivotal role in regulating these processes.

Magmenthanes A-H: Eight new meroterpenoids from the bark of Magnolia officinalis var. Biloba

Eight new meroterpenoids with different types of monoterpene units, namely, magmenthanes A-H (1–8), were identified from the bark of Magnolia officinalis var. biloba. Magmenthane A (1) possesses a 1,3-dioxabicyclo [4.3.01,5] nonane skeleton, 1–5 possess five pairs of enantiomers and 6 possesses a 1,1′-diallyl-biphenyl fragment. The structures of 1–8 were elucidated on the basis of 1D and 2D NMR, HRESIMS and electronic circular dichroism (ECD) calculations. Compounds 5 and 8 displayed significant PTP1B inhibitory activities with IC50 values of 4.38 and 3.88 μM, respectively.

The Protective Effect of Magnolol in Osteoarthritis: In vitro and in vivo Studies.

Osteoarthritis (OA), defined as a long-term progressive joint disease, is characterized by cartilage impairment and erosion. In recent decades, magnolol, as a type of lignin extracted from Magnolia officinalis, has been proved to play a potent anti-inflammatory role in various diseases. The current research sought to examine the latent mechanism of magnolol and its protective role in alleviating the progress of OA in vivo as well as in vitro experimentations. In vitro, the over-production of Nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), induced by interleukin-1 beta (IL-1β), were all inhibited notably by magnolol in a concentration-dependent manner. Moreover, magnolol could also downregulate the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5). All these changes ultimately led to the deterioration of the extracellular matrix (ECM) induced by IL-1β. Mechanistically, magnolol suppressed the activation of PI3K/Akt/NF-κB pathway. Furthermore, a powerful binding capacity between magnolol and PI3K was also revealed in our molecular docking research. In addition, magnolol-induced protective effects in OA development were also detected in a mouse model. In summary, this research suggested that magnolol possessed a new therapeutic potential for the development of OA.

Magnolia officinalis reduces the long-term effects of the status epilepticus induced by kainic acid in immature rats

During critical periods of neurodevelopment, the immature brain is susceptible to neuronal hyperexcitability, alterations such as hyperthermia, hypoxia, brain trauma or a preexisting neuroinflammatory condition can trigger, promote and prolong epileptiform activity and facilitate the development of epilepsy. The goal of the present study was to evaluate the long-term neuroprotective effects Magnolia officinalis extract, on a model of recurrent status epilepticus (SE) in immature rats. Sprague-Dawley rats were treated with kainic acid (KA) (3 mg/kg, dissolved in saline solution) beginning at day 10 P N every 24 h for five days (10 P N–14PN). Two experimental groups (KA) received two treatments for 10 days (14–24 P N): one group was treated with 300 mg/kg Magnolia Officinalis (MO) (KA-MO), and another was treated with 20 mg/kg of celecoxib (Clbx) (KA-Clbx) as a control drug. A SHAM control group at day 90 P N was established. Seizure susceptibility was analyzed through an after-discharge threshold (ADT) evaluation, and electroencephalographic activity was recorded. The results obtained from the ADT evaluation and the analysis of the electroencephalographic activity under basal conditions showed that the MO and Clbx treatments protected against epileptiform activity, and decreases long-term excitability. All rats in the KA-MO and KA-Clbx groups presented a phase I seizure on the Racine scale, corresponding to the shaking of a wet dog. In contrast, the KA group showed phase V convulsive activity on the Racine scale. Similarly, MO and Clbx exerted neuroprotective effects on hippocampal neurons and reduced gliosis in the same areas. Based on these results, early intervention with MO and Clbx treatments to prevent the inflammatory activity derived from SE in early phases of neurodevelopment exerts neuroprotective effects on epileptogenesis in adult stages.

Medication regularities of traditional Chinese medicine formulas for six kinds of pains by data-mining approach

To study and compare the medication regularities of traditional Chinese medicine formulas(TCMFs) for the six kinds of pains,namely abdominal pain,headache,epigastric pain,hypochondriac pain,heartache and backache,using a data-mining approach,in order to provide reference for relevant studies for the compatibility mechanism and new compound development of related TCMFs. A total of 2 443 TCMFs for pains were collected from the Dictionary of Chinese Medicine Prescriptions,and analyzed using the Apriori algorithm based on three indicators,namely confidence,lift and support,so as to study pivotal traditional Chinese medicines(TCMs) for each pain and their compatibility regularities. The results showed that deficiency tonifying medicines(such as Glycyrrhizae Radix et Rhizoma and Angelicae Sinensis Radix),Qi-regulating medicines(like Aucklandiae Radix) and blood circulation promoting medicines(like Chuanxiong Rhizoma) were commonly used TCMs for pains. However,there were many differences between drugs for various kinds of pains. For example,Magnoliae Officinalis Cortex was used frequently for abdominal pain and epigastric pain,while Saposhnikoviae Radix was used frequently for headache. The latent association rules with significant lift included Carthami Flos → Angelicae Sinensis Radix for abdominal pain,Astragali Radix → Glycyrrhizae Radix et Rhizoma for headache,Hordei Fructus Germinatus → Citri Reticulatae Pericarpium for epigastric pain,Gentianae Radix et Rhizoma → Bupleuri Radix for hypochondriac pain,and Caryophylli Flos → Moschus for backache. This study showed that based on the TCMFs from the Dictionary of Chinese Medicine Prescriptions,the data-mining approach can reveal the differences and similarities in the use of TCMs for the six kinds of pains,and discover the latent composition regularities of relevant TCMs.

Suppression of TRPV1 and P2Y nociceptors by honokiol isolated from Magnolia officinalis in 3rd degree burn mice by inhibiting inflammatory mediators

Burn pain is one of the worst imaginable pain, associated with considerable morbidity and mortality worldwide. The management of pain made significant progress; however, more research is needed for burn pain. In the present study, the antinociceptive effect of honokiol extracted from Magnolia officinalis was assessed for 3 consecutive days. The third-degree burns were induced by the hot water method. The honokiol both by intraperitoneal (i.p) and intra plantar (i.pl) route and in combination with tramadol (i.p) was found to be effective in significantly reducing the mechanical allodynia, hyperalgesia, thermal hyperalgesia and paw edema. Honokiol also succeeded in reducing weight loss and spontaneous pain behavior in mice. Honokiol treatment both i.p and ipl decrease significantly the loss of total protein (3.3 and 3.4 g/dl of total protein) and albumin (2.2 and 2.6 g/dl of total albumin) respectively. It also significantly recovers the normal balance of blood electrolytes and normalizes blood profile. Effect of honokiol on cytokines and mRNA expression levels of TRPV1 and P2Y were also assessed. Honokiol significantly decreases the expression of TNF-α, IL-1β and IL-6 and decreases expression level of TRPV1 and P2Y. Additionally, TRPV1 and P2Y proteins expression levels were also assessed by Western blot in paw skin tissue, sciatic nerve and spinal cord which were remarkably down-regulated by honokiol. Histological analysis of vehicle control and drug-treated paws were also performed through hematoxylin and eosin (H&E) staining which exhibited that honokiol significantly reduced the dermal layers distortion and inflammation associated with the burn. The antioxidant enzymes and nitric oxide (NO) were also determined through ELISA. Honokiol treatment also potentiates the expression of reduced glutathione and glutathione S-transferase, and catalase levels and reduced significantly the nitric oxide (NO) as compared to the burn-induced group. It can be concluded on the base of the results that honokiol has a significant analgesic activity through its action on cytokines and by downregulating TRPV1 and P2Y receptors. It also has a protective role against burn damage by upregulation of antioxidants.

Honokiol induces apoptotic cell death by oxidative burst and mitochondrial hyperpolarization of bladder cancer cells.

Bladder cancer is one of the most common types of malignant tumor worldwide. Current treatments, including chemo-/radiotherapy, only have limited efficacy on bladder cancer progression. Honokiol is an active component of Magnolia officinalis with multiple biological effects that may provide promising health benefits. In the present study, the anti-cancer properties of honokiol against bladder cancer cells were investigated by flow cytometric analysis. The results revealed that honokiol exhibited significant anti-proliferative effects on bladder cancer cell lines, particularly on BFTC-905 human transitional cell carcinoma cells. Furthermore, honokiol at low doses (≤25 µM) induced cell cycle arrest in G0/G1 phase, while it induced significant apoptotic cell death at high doses (≥50 µM; P<0.05). Furthermore, a significant accumulation of reactive oxygen species was identified in honokiol-treated cells. In addition, honokiol induced hyperpolarization of the mitochondrial membrane, which may lead to mitochondrial dysfunction. Finally, caspase-3/7 activation was identified in high-dose honokiol-treated bladder cancer cells. These results suggest that honokiol induces apoptosis via the mitochondrial pathway and honokiol-containing traditional herbal remedies may have a potential clinical application in the treatment of bladder cancer.