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Life
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Regulation of Natural Products to Immunity
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Regulation of Natural Products to Immunity

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (12 November 2021) | Viewed by 25585

Special Issue Editors

Dr. Chi-Chien Lin

E-Mail Website
Guest Editor
Institute of Biomedical Science, The iEGG and Animal Biotechnology Center, National Chung-Hsing University, Taichung 402, Taiwan
Interests: Immuno-oncology; autoimmunity; bioactive natural/organic synthetic pharmaceuticals
Special Issues, Collections and Topics in MDPI journals
Dr. Shih-Chao Lin

E-Mail Website
Guest Editor
Bachelor Program in Marine Biotechnology, College of Life Sciences, National Taiwan Ocean University, Keelung, Taiwan
Interests: marine viruses; antivirals; marine biotechnology
Special Issues, Collections and Topics in MDPI journals
Dr. Brian Carey

E-Mail
Guest Editor
United States Army Medical Research Institute of Infectious Disease, Fort Detrick, MA, USA
Interests: microbiology; virology; infectious disease; vaccine design; diagnostics

Special Issue Information

Dear Colleagues,

Evolutionary immunity plays a critical role in supporting healthy organisms, but immune responses could serve as a double-edged sword that could harm to the hosts when aberrant. An orchestrated immune system not only provides protection from pathogenic infection for its host, but also prevents distorted and overwhelming responses from damaging normal physiological functions.

Natural products generally derived from plants and microorganisms are regarded as a useful resource when looking for alternative remedies. These newly discovered natural compounds likely possess multiple bioactivities, including the regulation of host immunity. Therefore, it is essential to understand and illuminate the detailed relationship between natural products and their immunomodulatory effects. This being considered, we would like to invite researchers from all over the world to submit and share their studies regarding, but not limit to, the following topics to this Special Issue of Life:

  1. Isolation and identification of natural products from environment, plants, microorganisms, or animals with immunoregulatory activities.
  2. Elucidation of the interaction between a natural products and molecular mechanisms to regulate immune cells.
  3. Applications of immunomodulatory natural products in immunological diseases as potential treatments.
  4. Discovery of a new role of immunomodulatory natural products directly or indirectly in inhibition of pathogens.
  5. Computational analyses towards the micro-interaction between natural products and innate or adaptive immunologic receptors and/or signal transduction.

Prof. Chi-Chien Lin
Prof. Shih-Chao Lin
Dr. Brian Carey
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural product
  • immunoregulatory activities
  • mechanisms
  • therapy
  • pathogens
  • computational analyses

Published Papers (8 papers)

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Research

14 pages, 2017 KiB  
Article
Hesperidin and Chlorogenic Acid Synergistically Inhibit the Growth of Breast Cancer Cells via Estrogen Receptor/Mitochondrial Pathway
by Pang-Hung Hsu, Wei-Hsuan Chen, Chen Juan-Lu, Shu-Chen Hsieh, Shih-Chao Lin, Ru-Tsun Mai and Shiow-Yi Chen
Life 2021, 11(9), 950; https://doi.org/10.3390/life11090950 - 10 Sep 2021
Cited by 20 | Viewed by 3235
Abstract
Breast cancer is the most common cancer in women worldwide. Hesperidin (Hes) and chlorogenic acid (CA) are traditional medicinal molecules that abundantly exist in natural plants or foods. These compounds have been shown to prevent and suppress various cancers and therefore can be [...] Read more.
Breast cancer is the most common cancer in women worldwide. Hesperidin (Hes) and chlorogenic acid (CA) are traditional medicinal molecules that abundantly exist in natural plants or foods. These compounds have been shown to prevent and suppress various cancers and therefore can be utilized as adjunctive therapies to aid cancer treatment. Here, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays show a greater synergistic inhibitory effect on the growth of breast cancer cells, MCF-7, but not normal breast cells, MCF-10A, than hesperidin or chlorogenic acid alone. We present the possible molecular signaling pathways in MCF-7 cells with or without herbal molecule treatments via proteomic approaches. The data were further analyzed by Ingenuity Pathway Analysis (IPA) and confirmed by quantifying mRNA associated with the estrogen-receptor signaling pathway and mitochondrial functions. We demonstrated that the expression of CYC1, TFAM, ATP5PB, mtATP6, mtDNA, and NRF-1 were decreased upon 12 h treatment, and subsequent ATP production was also significantly decreased at 24 h. These results identified a synergistic effect induced by combinational treatment with hesperidin and chlorogenic acid, which can regulate mitochondria and ATP production through the estrogen receptor pathway in MCF-7 cells. However, none of the treatments induced the generation of reactive oxygen species (ROS), suggesting that ROS likely plays no role in the observed pharmacological activities. Overall, our study sheds light on the adequacy of hesperidin and chlorogenic acid to serve as an adjunctive therapy when co-administrated with chemotherapy drugs in breast cancer patients. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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14 pages, 3169 KiB  
Article
Alantolactone Suppresses Proliferation and the Inflammatory Response in Human HaCaT Keratinocytes and Ameliorates Imiquimod-Induced Skin Lesions in a Psoriasis-Like Mouse Model
by Wen-Ho Chuo, Yu-Tang Tung, Chao-Liang Wu, Nicole R. Bracci, Yu-Kang Chang, Hung-Yi Huang and Chi-Chien Lin
Life 2021, 11(7), 616; https://doi.org/10.3390/life11070616 - 25 Jun 2021
Cited by 9 | Viewed by 2930
Abstract
Psoriasis is an immune-mediated inflammatory disease that affects 2% to 3% of the world population. Alantolactone, a sesquiterpene lactone, was isolated from Inula helenium and Radix inulae and has several biological effects, including antifungal, anthelmintic, antimicrobial, anti-inflammatory, antitrypanosomal, and anticancer properties. This study [...] Read more.
Psoriasis is an immune-mediated inflammatory disease that affects 2% to 3% of the world population. Alantolactone, a sesquiterpene lactone, was isolated from Inula helenium and Radix inulae and has several biological effects, including antifungal, anthelmintic, antimicrobial, anti-inflammatory, antitrypanosomal, and anticancer properties. This study aimed to evaluate the antipsoriatic potential of alantolactone in vitro and in vivo and to explore its underlying mechanisms. These results showed that alantolactone significantly attenuated IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokine-induced hyperproliferation in HaCaT keratinocytes. Moreover, M5 cytokines significantly upregulated the mRNA levels of TNF-α, IL-6, IL-1β, and IL-8. However, alantolactone attenuated the upregulation of these inflammatory cytokines. In addition, alantolactone was found to inhibit STAT3 phosphorylation and NF-κB p65 nuclear translocation in HaCaT keratinocytes. Furthermore, alantolactone treatment in mice significantly alleviated the severity of skin lesions (erythema, scaling and epidermal thickness, and inflammatory cell infiltration) and decreased the mRNA expression of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, IL-8, IL-17A, and IL-23) in an IMQ-induced-like mouse model. Therefore, our new findings revealed that alantolactone alleviates psoriatic skin lesions by inhibiting inflammation, making it an attractive candidate for future development as an antipsoriatic agent. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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14 pages, 2526 KiB  
Article
Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice
by Po-Chang Wu, Shih-Chao Lin, Lauren Panny, Yu-Kang Chang, Chi-Chien Lin, Yu-Tang Tung and Hen-Hong Chang
Life 2021, 11(6), 530; https://doi.org/10.3390/life11060530 - 07 Jun 2021
Cited by 1 | Viewed by 4131
Abstract
Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, [...] Read more.
Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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12 pages, 1814 KiB  
Article
The Enhancing Effect of Fungal Immunomodulatory Protein-Volvariella Volvacea (FIP-vvo) on Maturation and Function of Mouse Dendritic Cells
by Ju-Pi Li, Yi-Pang Lee, Jung-Chein Ma, Betty-Revon Liu, Nien-Tsu Hsieh, Dz-Chi Chen, Ching-Liang Chu and Ren-In You
Life 2021, 11(6), 471; https://doi.org/10.3390/life11060471 - 24 May 2021
Cited by 2 | Viewed by 2526
Abstract
Volvariella volvacea, also known as straw mushroom, is a common edible mushroom in Chinese cuisine. It contains many nutrients for human health. A fungal immunomodulatory protein (FIP) has been isolated from V. volvacea and named FIP-vvo. Although the regulatory effects of many FIPs [...] Read more.
Volvariella volvacea, also known as straw mushroom, is a common edible mushroom in Chinese cuisine. It contains many nutrients for human health. A fungal immunomodulatory protein (FIP) has been isolated from V. volvacea and named FIP-vvo. Although the regulatory effects of many FIPs on immunity have been identified, the impact of FIP-vvo in modulating dendritic cells (DCs), which play a key role to connect the innate and the adaptive immunity, is not known. In this study, we aim to study the effect of FIP-vvo on the DC maturation and function. We found that FIP-vvo slightly increased the generation of CD11c+ bone marrow-derived DC (BMDC). In addition, the surface expression of MHCII was promoted in BMDCs after the treatment of FIP-vvo, suggesting that FIP-vvo induces DC maturation. Furthermore, FIP-vvo enhanced the ability of BMDCs to activate antigen-specific T cell responses in vitro. In the in vivo study, the FIP-vvo treatment facilitated T cell response in lymph nodes. Therefore, for the first time, our data demonstrated that FIP-vvo promoted DC maturation and function and suggested that FIP-vvo could have benefits for human health by enhancing immunity. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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11 pages, 1875 KiB  
Article
Interleukin-6 and Interleukin-8 Regulate STAT3 Activation Migration/Invasion and EMT in Chrysophanol-Treated Oral Cancer Cell Lines
by Po-Chih Hsu, Yi-Hsuan Chen, Ching-Feng Cheng, Chan-Yen Kuo and Huey-Kang Sytwu
Life 2021, 11(5), 423; https://doi.org/10.3390/life11050423 - 05 May 2021
Cited by 16 | Viewed by 2767
Abstract
The tumor microenvironment plays a critical role in the control of metastasis. The epithelial–mesenchymal transition (EMT) is strongly associated with tumor metastasis, and consists of several protein markers, including E-cadherin and vimentin. We discovered that chrysophanol causes oral cancer cell apoptosis and the [...] Read more.
The tumor microenvironment plays a critical role in the control of metastasis. The epithelial–mesenchymal transition (EMT) is strongly associated with tumor metastasis, and consists of several protein markers, including E-cadherin and vimentin. We discovered that chrysophanol causes oral cancer cell apoptosis and the inhibition of migration/invasion and EMT. However, the detailed mechanisms of chrysophanol and its role in oral cancer with respect to the tumor microenvironment remain unknown. In the clinic, proinflammatory cytokines, such as IL-6 and IL-8, exhibit a higher expression in patients with oral cancer. However, the effect of chrysophanol on the production of IL-6 and IL-8 is unknown. We evaluated the expression of IL-6 and IL-8 in human SAS and FaDu oral cancer cell lines in the presence or absence of chrysophanol. The migration and invasion abilities were also determined using a Boyden chamber assay. Our results showed that treatment with chrysophanol significantly decreased the expression of IL-6 and IL-8, as well as the invasion ability of oral cancer cells. Moreover, chrysophanol also attenuated the EMT by increasing the expression of E-cadherin and reducing the expression of vimentin. Mechanistically, chrysophanol inhibited IL-6- and IL-8-induced invasion and STAT3 phosphorylation. IL-6 and IL-8 promote EMT and cell invasion, which is potentially related to the STAT3 signaling pathway in oral cancer. These findings provide insight into new aspects of chrysophanol activity and may contribute to the development of new therapeutic strategies for oral cancer. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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11 pages, 2428 KiB  
Article
Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages
by Chun-Yu Lin, Shih-Han Kao, Ling-Chien Hung, Hsin-Ju Chien, Wen-Hung Wang, Yu-Wei Chang and Yen-Hsu Chen
Life 2021, 11(5), 411; https://doi.org/10.3390/life11050411 - 30 Apr 2021
Cited by 8 | Viewed by 2323
Abstract
Sepsis develops from a serious microbial infection that causes the immune system to go into overdrive. The major microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved [...] Read more.
Sepsis develops from a serious microbial infection that causes the immune system to go into overdrive. The major microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved in the LPS-induced pro-inflammatory process. This study aimed to evaluate the effects of polyphenol Tellimagrandin II (TGII) on anti-inflammatory activity and its underlying basic mechanism in murine macrophage cell line RAW 264.7 and human monocyte-derived macrophages. Macrophages with more than 90% cell viability were found in the cytotoxicity assay under 50 μM TGII. Pre- or post-treatment with TGII significantly reduced LPS-induced inducible nitric oxide synthase (NOS2) protein and mRNA expression, reducing LPS-induced COX-2 protein. Downstream of NOS2 and COX-2, NO and prostaglandin E2 (PGE2) were significantly inhibited by TGII. Upstream of NOS2 and COX-2, phospho-p65, c-fos and phospho-c-jun were also reduced after pre-treatment with TGII. Mitogen-activated protein kinases (MAPKs) are also critical to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) stimulation, and phospho-p38 expression was found to have been blocked by TGII. TGII efficiently reduces LPS-induced NO production and its upstream regulatory factors, suggesting that TGII may be a potential therapeutic agent for sepsis and other inflammatory diseases. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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14 pages, 2954 KiB  
Article
Poria cocos Modulates Th1/Th2 Response and Attenuates Airway Inflammation in an Ovalbumin-Sensitized Mouse Allergic Asthma Model
by Chien-Liang Chao, Chao-Jih Wang, Hsin-Wen Huang, Han-Peng Kuo, Muh-Hwan Su, Hang-Ching Lin, Chia-Wen Teng, Leticia B. Sy and Wen-Mein Wu
Life 2021, 11(5), 372; https://doi.org/10.3390/life11050372 - 21 Apr 2021
Cited by 13 | Viewed by 3343
Abstract
Poria cocos, called fuling, is a famous tonic in traditional Chinese medicine that reportedly possesses various pharmacological properties, including anti-inflammation and immunomodulation. However, few studies have investigated the effects of P. cocos on allergic diseases, such as allergic asthma. Allergic asthma is [...] Read more.
Poria cocos, called fuling, is a famous tonic in traditional Chinese medicine that reportedly possesses various pharmacological properties, including anti-inflammation and immunomodulation. However, few studies have investigated the effects of P. cocos on allergic diseases, such as allergic asthma. Allergic asthma is caused primarily by Th2 immune response and characterized by airway inflammation. This study first demonstrated the anti-allergic and anti-asthmatic effects of P. cocos extract (Lipucan®). P. cocos extract distinctly exhibited reduced inflammatory cell infiltration in the peribronchial and peribronchiolar regions compared to the asthma group in the histological analysis of pulmonary tissue sections. Prolonged P. cocos extract administration significantly reduced eosinophil infiltration, PGE2 levels, total IgE, and OVA-specific IgE. Moreover, P. cocos extract markedly suppressed Th2 cytokines, IL-4, IL-5, and IL-10. On the other hand, P. cocos extract significantly elevated IL-2 secretion by Th1 immune response. In addition, P. cocos extract elevated the IFN-γ level at a lower dose. We also observed that P. cocos extract increased the activity of NK cells. Our results suggest that P. cocos extract remodels the intrinsic Th1/Th2 response to prevent or alleviate allergy-induced asthma or symptoms. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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10 pages, 423 KiB  
Article
The Lanostane Triterpenoids in Poria cocos Play Beneficial Roles in Immunoregulatory Activity
by Chien-Liang Chao, Hsin-Wen Huang, Muh-Hwan Su, Hang-Ching Lin and Wen-Mein Wu
Life 2021, 11(2), 111; https://doi.org/10.3390/life11020111 - 01 Feb 2021
Cited by 20 | Viewed by 3227
Abstract
Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This [...] Read more.
Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan®) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity. Full article
(This article belongs to the Special Issue Regulation of Natural Products to Immunity)
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