| Certification: | ISO, FDA, Hahal, Food Manufacturing License, Business Licens |
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| Assay Method: | HPLC, UV |
| Application Form: | Tablet, Capsule |
| Application: | Food, Health Care Products, Medicine |
| State: | Powder |
| Extract Source: | Dictyophora Indusiata (Vent.Ex Pers) Fisch) |
| Samples: |
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| Customization: |
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Audited Supplier | Product Name | Dictyophora Indusiata Extract |
| Botanical Name | Dictyophora indusiata (Vent.ex Pers) Fisch) |
| Part Used | Fruiting Body /Mycelium |
| Appearance | Brownish Yellow Powder |
| Specification | 4:1 10:1 Straight Powder |
| Storage Period | 24 Months |
| Package | 1kg/bag 25kg/drum |
| Storage Conditions | Store in cool and dry places. Keep away from strong light and heat. |
| Description Dictyophora indusiata (Vent.) Fisch. is an edible and medicinal mushroom that belongs to the family Phallaceae of the Agaricomycetes class (phylum Basidiomycetes) of fungi. In recent taxonomic literature, the synonym Phallus indusiata Vent. is the accepted name for the fungus though nearly all the scientific literature so far is available under the name entry of D. indusiata. As a saprophytic fungus, it grows in well-rotted woody trunk or rich soil of tropical Africa, Asia, Australia and the Americas. Its food and medicinal value are however much appreciated in the far eastern countries such as China where it grows on the wet roots of bamboo groves and in forests. Its common local names mainly in China and Japan include bamboo mushrooms, bamboo pith, long net stinkhorn, crinoline and stinkhorn basket, but perhaps the names most vividly associated with the morphologically distinctive feature of the fungus are bridal veil fungus, veiled lady or queen of the mushrooms. As shown in Figure 1, the fruiting body of D. indusiata has three macroscopic features: conical cap, a stalk and an indusium net-like white veil that hangs from the head/cap down to cover the leg/stalk. Hence, the name-veiled lady appears to be given to describe the skirt like appearance of the elegant fruiting body (Figure 1). Health Benefits 3.1. Antioxidant Effect In an experiment where hydroxyl radical (OH·) was generated through iron catalyzed H2O2 fission, the water-soluble polysaccharides have been shown to display free radical scavenging effect [14,35]. At concentrations far less than 1 mg/mL, the polysaccharides with direct scavenging effect against 1, 1-diphenyl-2-picrylhydrazyl (DPPH), OH· and superoxide (O2−) radicals have also been shown [18]. In many experiments, the aqueous extract and crude polysaccharide fractions have been shown to display radical scavenging effects up to the concentration of 2 mg/mL [53]. Consistent with these findings, ABTS+ and OH·, DPPH, and O2− radicals were suppressed wile lipid peroxidation was inhibited both by the water extract, crude polysaccharides and their sub-fractions [1,46]. The acid-extractable polysaccharides do also have similar effect in scavenging OH·, O2− and DPPH radicals when tested at the concentration range of 0.2-1.4 mg/mL [35]. In addition to similar radical scavenging effects, the reducing power of purified water soluble β-d-glucan polysaccharide was further shown [21]. In an attempt to improve the biological activities of the water-insoluble polysaccharides, the sulfated [43] and phosphorylated [13] derivatives have been prepared. In both cases, improvement in the antioxidant activity was observed for the derivatives along with improved water solubility. With the implication of improved bioavailability, it would be interesting to see the in vivo pharmacological activities of these phosphorylated/sulfated derivatives. In an oxidative hemolysis induced by 2-amidino-propane, a purified polysaccharide considered novel (DP1) has been shown to demonstrate antioxidant and anti-hemolytic effect at exceptionally low dose of 20 nmol/mL. While the level of lipid peroxidation (LPO) marker, malondialdehyde (MDA), and reactive oxygen species (ROS) were suppressed, the activities of intracellular antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were enhanced. Furthermore, the cupric chloride-induced conjugated diene formation in plasma was ameliorated by the DP1 [39]). The antioxidant activities of polysaccharides have also been demonstrated in animal models. Under parquet-induced oxidative conditions in Caenorhabditis elegans, D. indusiata polysaccharides could decrease ROS and MDA levels while enhancing SOD activity [19]. It also restored mitochondrial function and integrity as evidenced from, membrane potential and ATP content. The transcription factors SKN-1/Nrf2 and DAF-16/FOXO, which are associated with stress response and lifespan regulation, have been shown to be activated by D. indusiata polysaccharides. Readers should note that the skn-1 gene in C. elegans encodes a transcription factor that resembles the mammalian nuclear factor erythroid 2-related factor 2 (Nrf2). On the other hand, the DAF-16/FOXO transcription in C. elegans is the mammalian equivalent of the Forkhead transcription factors with the DNA binding domain or Forkhead box (FOX). This transcription factor is involved in diverse cellular function including the regulation cell death or apoptosis, resistance to oxidative stress and increased life span. Good references for the regulation of these transcription factors are available [54,55,56]. Hence, transcription factors that are critically involved in alleviation of oxidative stress and increased life span of C. elgans are activated by D. indusiata polysaccharides. In agreement with this data, the acidic and alkali extracted polysaccharides have been shown to increase SOD and GPx activities in the d-galactose-induced senescence in rats [22]. In high fat-induced oxidative damage model, the water soluble polysaccharides administered in mice could abolish the increased LPO (MDA level) while increasing the antioxidant status by elevating SOD, GPx, CAT and total antioxidant capacity (T-AOC) contents/activities in the liver and kidney tissues [14,35]. Similar with this observation was the study by Wang et al. that showed organoprotective (hepatoprotective) effect along with increased antioxidant status in obese and hyperlipidemic mice [48]. Other in vivo model for the demonstration of antioxidant effects was the colitis model in mice where intestinal oxidative stress as assessed by the increased MDA level and GSH depletion markers which were normalized by β-glucans [4]. More importantly, the protein expression level of the antioxidant hem oxygenase-1 (HO-1) was raised in colonic tissues. This is consistent with another study on colitis model in mice where the crude polysaccharides have been shown to enhance the level of SOD activities while lowering nitric oxide (NO) level in colonic tissues [49]. All these data reveal the potential therapeutic implication of D. indusiata polysaccharides in pathologies associated with ROS and/or oxidative stress. 3.2. Neuroprotective Effect and Potential Application in Neurodegenerative Diseases By using wild-type and transgenic C. elegans models, Zhang et al. [19] studied the neuroprotective effect of D. indusiata polysaccharides under various conditions. In addition to the above-mentioned antioxidant effects (see Section 3.1), the acidic polysaccharides have been shown to mitigate the polyglutamine and amyloid-β protein-induced chemosensory behavior dysfunction in transgenic nematode models of neurodegenerative disease. Hence, the antioxidant mechanism including the Nrf2 pathway and inhibition of the polyglutamine- and Aβ-mediated neurotoxicity suggest the potential therapeutic application of D. indusiata for neurodegenerative diseases. The reversal of oxidative stress by acidic and alkali extracted polysaccharides of D. indusiata in d-galactose-induced senescence in mice [22] also imply potential amelioration of age-related disorders such as Alzheimer's disease. The small molecular weight compounds of D. indusiata have not yet been extensively studied for their neuroprotective effects. In the study by Kawagishi et al. [24], the eudesmane-type sesquiterpenes isolated from the aqueous alcohol (74% ethanol) extract were assessed for their potential effect on astroglial cells. They have shown that they could enhance the synthesis and subsequent release of NGF by four-fold when the cells were treated by dictyophorine A (3.3 μM). Since dictyophorine B was active, but with less potency, the epoxy functional group in these eudesmane-type compounds (Figure 4) appears to be an important structural feature for NGF release. The role of NGF and agents that promote its release and function as potential therapeutic agents for Alzheimer's disease and related neurodegenerative diseases have been extensively reviewed [57]. On the basis of the in vitro data, more research on the mechanisms and in vivo effect of dictyophorine A, or D. indusiata extracts as neuroprotective agents, is therefore well justified. In their pioneering work, Lee et al. [26] were the first to characterize and establish the neuroprotective effect of dictyoquinazols that they isolated and characterize from D. indusiata. The compounds (dictyoquinazol A, B, and C, Figure 6) were able to protect primary mouse cortical neurons from excitotoxicity and cell death induced by glutamate and NMDA. More importantly, the dose-dependent effect was evident in the lower μM concentration range (up to 5 µM). 3.3. Anticancer Effect The direct cytotoxic effects of the polysaccharides against cancer cells may be seen as generally weak and occur at higher μM concentration at best. The triple helical polysaccharide (PD3), for example, did not display cytotoxicity against mouse sarcoma S180 cells in vitro when tested up to 1 mg/mL though it displayed impressive effect in vivo [15]. In contradiction to this observation, however, the crude polysaccharide has been shown to display direct cytotoxicity in the same cell line, osteosarcoma S180 cells [45]. This effect was also seen at moderate concentration range of 10-160 μg/mL. The dose-dependent effect was also in line with induction of apoptosis as evidenced from morphological, biochemical and gene expression analysis (Table 1). Other studies also showed the direct cytotoxic effects of the water extract and crude polysaccharides against HeLa and HepG2 cells within the concentration range of 100-600 μg/mL [46]. To enhance the cytotoxic activity of the purified polysaccharide, DP1, Liao et al. [41] also prepared a zinc chelate product. The direct cytotoxicity of this derivative against MCF-7 cells was shown through induction of apoptosis as evidenced through the classical DNA fragmentation, cell cycle arrest (S-phase) and activation of caspases (caspases-3, -8, and -9). A further possible mechanism for the induction of apoptosis was mitochondrial dysfunction and ROS overproduction induced by the zinc chelate of DP1. Induction of ROS overproduction through the mitochondrial respiratory pathways leading to caspases activation and apoptosis appears to be consistent to the anticancer activity of many natural products [58]. The same group also prepared a monodispersed selenium nanoparticle of DP1 that induce apoptosis in HepG2 cells through exactly the same above-mentioned mechanism [40]. Other derivatization studies were based on phosphorylated and sulfated products which showed more cytotoxic effect against MCF-7 and B16 cells than the parent polysaccharides [13,43]. A further advantage of this approach lies on the water solubility of the sulfated/phosphorylated derivatives as compared to the water insoluble starting material which may have relevance to in vivo applications. Several animal experiments have also been employed to demonstrate the potential anticancer effect of D. indusiata polysaccharides. In S180 tumor bearing mice, the triple helical polysaccharide (PD3) administered intraperitoneally (i.p.) for ten days has been shown to suppress tumor size and reverse body weight loss [15]. This could be partly due to the immunostimulant effect of the polysaccharide (see Section 3.4). Both β-(1→3)-D-glucans and α-(1→3) linked D-mannan polysaccharides from D. indusiata have also been shown to suppress tumor growth in S180 tumor bearing mice [51]. The maximum doses employed as 25 mg/kg via the i.p. route is also encouraging for further studies in this field. 3.4. Immunomodulatory Effect Readers should make the distinction between therapeutic application via an immunestimulatory effect and immunosuppression. Polysaccharides could do both, and while immunostimulation is applicable when the immune system is suppressed such under cancer pathology, immunosuppression is applicable under chronic inflammatory conditions such as colitis, sepsis, etc. The effect of D. indusiata compounds described in the following sections under these two contrasting conditions should not therefore be seen as a contradiction. 3.4.1. Immunostimulation The immunestimulatory effect of D. indusiata polysaccharides has been demonstrated in unstimulated macrophages in vitro. Treatment of the murine RAW264.7 cells with these polysaccharides could induce a proliferative response while markers of macrophage activation such as cytokines (IL-1β, IL-6 and TNF-α), NO synthase (level of NO) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) p65 were upregulated [38]. Moreover, macrophage activation by these polysaccharides could be attributed to the toll-like receptor 4 (TLR4) since the observed activity could be abolished by anti-TLR4 and anti-CR3 mAbs. In another study by the same authors, one purified polysaccharide (Dectin-1) was shown to induce other markers of macrophage activation in RAW264.7 cells including pseudopodia formation, cell spreading and phagocytosis [20]. In addition to the above-mentioned specific binding to TLR4, cytokine (IL-1β and TNF-α) expression, and NF-κB activation and nuclear translocation, Dectin-1 has been shown to induce the phosphorylation of the extracellular signal-regulated kinase 1/2 (ERK1/2), JNK1/2 and p38 mitogen-activated protein kinase (MAPK) [20]. As part of the immunostimulation process, macrophage activation with specific recruitment of M1-phenotype leading to tumour suppression has been shown to be a function of these MAPKs activation [59]). It has also been shown that the immunestimulatory effect of polysaccharides like that obtained from Laminaria japonica is through TLR4 as a recognition receptor leading to ERK1/2, JNK1/2 and P38 activation, NF-κB p65 mobilization from the cytoplasm to nucleus, and cytokines and NO overproduction in macrophages [60]. The study by Fu et al. [44] on immunestimulatory effect of the polysaccharides were similar with the above studies by Deng et al. [20,38]. They have shown however that the purified polysaccharide of β-(1→3)-glucan with side branches of β-(1→6)-glucosyl unit had a triple-helical structure. It promoted the proliferation of RAW 264.7 macrophage along with induction of NO and cytokine (TNF-α, IL-1, IL-6, and IL-12) production. Animal experiments using the acid and alkali extractible polysaccharides also showed increased macrophage phagocytosis power and NK cells killing activity (only for the alkali extract) [44]. A classic example of immnunostimulation and a further potential application of D. indusiata polysaccharides to cancer therapy was highlighted by the study of Han et al. [37] which employed the supernatant of prostate cancer fibroblasts to suppress immune cells. Under this condition, they have shown that the polysaccharides could stimulate lymphocyte proliferation and could ameliorate the suppressed growth of CD4+/CD8+ T cells. As a direct link between cancer and immunosuppression, the potential effect of triple helical polysaccharide (PD3) was also assessed in ascitogenous sarcoma S180 bearing mice [15]. The tumor suppressive effect of this polysaccharide was shown to be associated with increased level of cytokines in the blood such as IL-2, IL-6, and TNF-α. 3.4.2. General Anti-Inflammatory, Immunosuppressive and Effect on the Gut Microbiota Wang et al. [36] employed the classical LPS-stimulated macrophage activation assay to assess the anti-inflammatory potential of D. indusiata polysaccharides. At fairly small doses (25-50 μg/mL), the LPS-induced cytokine (IL-1) and ROS production, as well as TLR4 expression and NF-κB activation/nuclear translocation, were suppressed. By using the carrageenan-induced oedema model of the classical inflammation model and scalded edematous hyperalgesia in rats' hind paws, Hara et al. [52] were the first to demonstrate the ant-inflammatory potential of D. indusiata β-glucans. One of the best anti-inflammatory activity studies for the D. indusiata β-glucans was based on the dextra sulphate sodium (DSS)-induced colitis model in mice [4]. In this study, oral administration of up to the maximum doses of only 100 mg/kg effectively reversed colonic length and inflammatory and oxidative markers (Table 2). Of the inflammatory markers suppressed were cytokines' gene expression for TNF-α, IL-6, IL-1β and IL-18 and myeloperoxidase (MPO) activity. At the biochemical level, apoptosis markers were suppressed, tight junction proteins (TJP-1 protein expression) were abundant, the expressions for nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3), phosphorylated signal transducer and activator of transcription 3 ((p)-STAT3) and p-IκBα (phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) enhanced, and M1 macrophage (F4/80+CD11b+ cells) polarization were down-regulated while the M2 (F4/80+CD206+ cells) subsets in splenic tissues were raised. Another study using the DSS-induced colitis model in mice was that employed by Kanwal et al. [49] where the crude polysaccharide at a maximum oral dose of only 33 mg/kg was tested. In addition to amelioration of the physical markers of colitis (Table 2), the enhanced mucins and tight junction proteins expressions along with improved antioxidant status were evident. As an anti-inflammatory agent, the crude polysaccharides also suppressed the levels of proinflammatory cytokines and MPO activity, boost the level of anti-inflammatory cytokines, and ameliorate the expression of iNOS and NFκB activation. In addition to the above-mentioned anti-inflammatory properties of D. indusiata polysaccharides in the ulcerative colitis model demonstrated by Wang et al. [4], the decrease in the abundance of Firmicutes and increased Proteobacteria levels under a similar DSS-induced colitis model in mice were reversed by the administration of the crude polysaccharides [49]. Another comprehensive study on the effect of D. indusiata polysaccharides on gut microbiota came from the study by Kanwal et al. [7]. Under broad-spectrum antibiotic-mediated dysbiosis and intestinal barrier dysfunction, D. indusiata polysaccharides have been shown to recover the altered (Firmicutes/Bacteroidetes ratio and increased the relative abundance of harmful flora such as Proteobacteria, Enterococcus, and Bacteroides) gut microbiota composition. More specifically, they have reported that the polysaccharides enhance the level of beneficial flora, such as Lactobacillaceae (lactic acid-producing bacteria), and Ruminococaceae (butyrate-producing bacteria). Moreover, the lipopolysaccharides were shown to suppress endotoxemia and the level of pro-inflammatory cytokine TNF-α, IL-6, and IL-1β, while the expression of tight-junction associated proteins (claudin-1, occludin, and zonula occludens-1) were increased. All these anti-inflammatory effects coupled with improvement of the gut microbiota and restoration of tight junction and mucus barriers demonstrated by Kanwal et al. [49] imply the potential immunomodulatory effect of D. indusiata polysaccharides. 3.5. Antiobesity and Potential Antidiabetic Effect The comprehensive antiobesity potential study by Wang et al. [14,35] employed a high fat-induced obesity model where the water-extractible polysaccharides of D. indusiata were administered in mice orally for 45 days. As shown in Table 2, the obesity-induced hypercholesterolemia, increased liver enzyme markers in the serum, and liver and kidney morphological changes and oxidative stress were ameliorated. These activities imply a wider effect of organoprotective effect primarily where oxidative stress is implicated and also in obesity-associated diseases like diabetes and cardiovascular complications. Wang et al. [48] also employed the high-fat-induced obesity and hyperlipidemia model to assess the potential antidiabetic effects of D. indusiata polysaccharides obtained by enzyme assisted or alkali extraction method (Table 2). They have demonstrated a direct glucose lowering effects under OGTT while the alteration in the serum adiponectin level and the increases in insuli and leptin were normalized. All these data [47] were in addition to the antioxidant, organoprotective (hepatocytes), antiobesity (weight gain reduction) and antihyperlipidemic effect (Table 2), which were also reported previously [14,35]. As the obesity associated alteration in the level of urea, creatinine, albumin, insuli, leptin and adiponectin were reversed by the polysaccharides [14,35,47], a further comprehensive study on the antidiabetic potential of D. indusiata polysaccharides is well merited. 3.6. Antibacterial Effects Chen et al. [25] described the isolation and characterization of the antibiotic albaflavenone from D. indusiata which has been widely known for its antibacterial activities. As a component of Streptomyces (e.g., Streptomyces albidoflavus, S. coelicolor), its biosynthesis pathway and activities have been the subject of many studies [61,62,63,64]. As part of the antioxidant and antimicrobial activity study, Oyetayo et al. [53] also reported that the water extract of D. indusiata can inhibit the growth of bacteria and fungi. The reported activity was however not of therapeutic relevance and was 200 mg/mL. Since the known antibiotic principle is a lipophilic terpenoid, albaflavenone, the poor antimicrobial activity of the water extract only suggests the lack of water soluble antibiotic agent in the fungi. 3.7. Other Effects 5-(hydroxymethyl)-2-furfural isolated from the methanolic extract of D. indusiata has been shown to display tyrosinase inhibitory effect in a non-competitive manner [29]. In view of the functional role of tyrosinase enzyme in melanogenesis, insect metabolism and fruits and vegetables spoilage due to browning and taste change, its inhibitors have long been appreciated in the medical, cosmetics and agrochemical industries. Numerous natural products such as phenolics and the gold standard reference compound, kojic acid, are known for their tyrosinase inhibition. Sharma et al. [29] also screened three analogues of 5-(hydroxymethyl)-2-furfural (Figure 7) for their tyrosinase inhibitory effect. Furfural (IC50, 0.35 mM) but not 2-furoic acid was active suggesting the role of the aldehyde functional group for the observed activity. On the other hand, 5-methyl furfural (IC50, 0. 76 mM) had comparable inhibitory effect as 5-(hydroxymethyl)-2-furfural (IC50, 0.98 mM). We should note however that this level of potency and the non-competitive nature of inhibition do not make 5-(hydroxymethyl)-2-furfural as a significant lead compound for the discovery of novel tyrosinase inhibitors as depigmentation agents in medicine/cosmetics or anti-browning agents in the food/agricultural industries. Wang and Ng [65] isolated a 28 kDa ribonuclease (RNase) with specific activity of 564 U/mg towards yeast transfer RNA. The potential effect of the RNase in other fields need to be assessed given other RNase from mushrooms such as Hohenbuehelia serotina have been shown to inhibit the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and inhibit leukemia (L1210) cells and lymphoma (MBL2) cells proliferation [66]. |
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