Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease
Abstract
:1. Introduction
1.1. Respiratory Disease Pathology and Epidemiology
Respiratory Disease * | Disease Classification | Causative/Risk Factors | Predominant Symptoms | Estimated Worldwide Morbidity (Annual) (P: Prevalence, I: Incidence) | Estimated Worldwide Mortality (Annual) | Conventional Treatments | Trends | Ref |
---|---|---|---|---|---|---|---|---|
Infectious diseases (e.g., TB; NTM; influenza; pneumonia †; corona viruses) | - Communicable ‡ - Acute - May become chronic if unresolving or recurrent | - Opportunistic bacterial; viral; fungal or parasitic invasion - Risk factors: low immunization rates; overpopulation; conditions of compromised immunity | Inflammation; cough; increased mucus; fever; dyspnea; tachypnea; malaise; muscle and join pain; sore throat; secondary infections | - TB: 10 million (P) - NTM: 40 per 100,000 population (P) - Influenza: 5–15% of population; 3–5 million severe cases (I) - RSV: 34 million child episodes (I) - COVID-19: >56 million § (P) | - >4 million total ¶ - TB: 1.5 million - Pneumonia: >1.3 million children <5 y (15% of all deaths) - Seasonal influenza: 290,000–650,000 - COVID-19: 1,500,000 § | - Antibiotics (bacterial) - Neuraminidase inhibitors (viral) - Symptomatic treatment - Immunization | - Consistently within top 3 causes of death - TB incidence declining by 2%/y, NTM increasing 40%/y - Increasing epidemics and drug resistant strains - Highest impact in developing countries | [2,26,27,28] |
Chronic obstructive pulmonary disease (COPD) | - Non-communicable ‡ - Chronic with acute episodes - Progressive - Irreversible | - Tobacco smoke and other inhaled environmental pollutants - Frequent/chronic lower respiratory infections, asthma and abnormal lung development - Genetic factors | Chronic parenchymal and airway inflammation; persistent airflow restriction; dyspnea; wheeze; cough; decreased airway elasticity; airway remodeling; mucociliary dysfunction; co-morbidities | - >250 million (P) - Usually becomes apparent in people >40 yes of age | - 3.2 million - Third leading cause of death | - Cessation of smoking - Symptomatic treatment - Inhaled corticosteroids; long-acting β agonists; leukotriene modifiers - Immunization against infectious diseases | - Increasing prevalence and mortality rates | [2,27,29] |
Asthma | - Non-communicable - Chronic with acute episodes - Reversible | - Genetic factors - Environmental triggers - Airway hyperresponsiveness | Airflow restriction; wheeze; dyspnea; cough; airway remodeling | - >339 million (P) - 24.8 million DALYs lost | - Relatively low mortality rate - 420,000 (2016) | - Medications for: rescue (e.g., fast-acting β agonists), maintenance (e.g., inhaled corticosteroids; long-acting β agonists; leukotriene modifiers) and allergies - Avoidance of triggers | - Increasing incidence - Highest mortality (80%) in developing countries | [2,5,27,30,31] |
Lung cancer | - Non-communicable - Chronic - Progressive | - Tobacco smoke and other inhaled environmental pollutants - Physical carcinogens (e.g., ionizing radiation) - Other chronic respiratory diseases - Genetic factors | Dyspnea; hoarseness; hemoptysis; pain; loss of appetite; weight loss; fatigue; persistent cough | - 2.09 million (P) - 1.8 million (I) | - 1.76 million | - Surgery - Radiation and chemotherapy - Palliative care and psycho-social support | - 15% of diagnosed cancers - Most fatal cancer - 19% of deaths | [2,6,27] |
Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) | - Non-communicable - Acute | - Trauma - Pulmonary infection - Non-pulmonary sepsis - Certain medical procedures | Severe dyspnea and tachypnea; pulmonary hemorrhage; edema; hypertension; hypoxemia; tissue damage; fibrosing alveolitis | - ARDS: 58.7–75 per 100,000 people (I) - ALI: 78.9 per 100,000 people (I) | - In-hospital mortality 38% for ALI; up to 46.1% for ARDS | - Corticosteroids and other anti-inflammatories; vasodilators - Mechanical ventilation - Hemodynamic management - Surfactant therapy | - 10% of all patients in intensive care treated for ARDS - Survival rates improving | [11,19] |
Cystic fibrosis | - Non-communicable - Chronic with acute episodes - Progressive | - Autosomal recessive genetic factors (CFTR mutation) - Exacerbated by environmental triggers and infection # | Bronchiecstasis; persistent airway infection and inflammation; excessive, thick mucus and poor clearance; pneumothorax; hemoptysis; tissue damage; gastrointestinal, metabolic and reproductive manifestations | - 90,000 (P) (likely underestimated) - 1000 (I) | - More than half of patients die before the age of 18 | - Antibiotics - Immunisations - Nebulised hypertonic saline; dornase alfa; mannitol - CFTR modulators (e.g., Ivacaftor) - O2 therapy; pulmonary rehab. - Management of co-morbidities and nutrition - Lung transplant | - Survival rates improving | [32] |
1.2. Conventional Treatments and the Need for Alternatives
1.3. Molluscs: A Wealth of Potential Therapeutic Compounds
2. Literature Search Methods and Evaluation
3. Uses of Molluscs in Traditional Medicines for Respiratory Disease
3.1. Traditional Molluscan Respiratory Medicines
Respiratory Disease or Symptom | Words/Phrases Used in the Literature to Describe Symptom or Disease | No. of Remedies * | No. of Species | Mollusc Parts Used | Cultures/Traditional Medicine Systems | Ref. |
---|---|---|---|---|---|---|
Allergy | Allergy; hypersensitivity; ENT or pulmonary allergies | 10 | 2 | Egg masses; flesh; whole animal; ink; shell | Europe; China | [104,118,119,120] |
Asthma | Asthma; shortness of breath; dyspnea; wheeze; asthmatic cough; dyspnea with cough | 19 | 46 | Body; foot; shell; pearl; eggs | China; India; South America; Middle East | [78,91,110,113,114,115,118,119,120,121,122,123,124,125] |
Cancer | Cancer; tumor; neoadjuvant treatment | 4 | 17 | Flesh; shell; operculum | India; South America; Egypt; China | [104,113,114,126,127] |
Cough | Cough; chesty cough; croup; hemoptysis; laryngismus; whooping cough; cough associated with infection or fever; cough associated with inflammatory conditions; nervous cough; cough with chest stuffiness and dyspnea; xeropulmonary cough; cough and regurgitation | 28 | 127 | Adductor muscle; egg masses; flesh; mucus; pearl; shell | China; Europe; India; South America; Middle East; Nigeria | [91,113,114,123,124] |
Ear problems | Ear problems; ear pain; ear inflammation; ear ache; ottorhoea; otitis media; parotid gland swelling and hearing loss; ear and eye diseases | 9 | 14 | Flesh; mucus; shell; operculum | China; Europe; India; Egypt; Nigeria | [104,109,114,118,119,120,123,126,127] |
Fever | Fever; high fever; low fever; fever in children; fever and convulsion in children; high fever; feverish sensation in chest; night sweating; heat; heat toxicity | 15 | 59 | Adductor muscle; flesh; pearl; shell; whole animal | China; Europe; India; Korea | [91,104,109,114,128] |
Low immunity | Strengthens immune system | 3 | 3 | Flesh; shell | Europe | [109] |
Infection † | Infection; pneumonia; measles; flu; bronchitis; anthrax; upper respiratory tract infections in children; infectious diseases; bronchitis; measles; conjunctive congestion with swelling and pain | 18 | 56 | Flesh; shell; mucus; whole animal | China; Europe; South America; India | [91,109,113,114,118,119,120,129] |
Respiratory inflammation | Inflammation; sinus inflammation; inflammatory conditions; parotid gland swelling; acute and chronic chest ailments; edema; swelling and pain; acute and chronic sinusitis | 10 | 36 | Flesh; shell; mucus; whole animal; operculum | China; Europe; India | [91,109,114,123] |
Mucus | Mucus; excessive mucus; phlegm; congestion; nasal congestion; used as expectorant; retention of phlegm and fluid; phlegmatic heat; retention of fluid in chest | 22 | 101 | Adductor muscle; flesh; operculum; pearl; shell | China; Europe; India | [109,114,118,119,120] |
Sore throat | Sore throat; pharyngitis; hoarseness; tonsillitis; tracheitis; pharynalgia | 10 | 21 | Flesh; mucus; shell; whole animal; pearl | China; Europe; South America; India | [91,114,130] |
Tuberculosis ‡ | Tuberculosis; pthisis; scrofula; pulmonary tuberculosis; tuberculosis of lymph nodes | 47 | 237 | Adductor muscle; egg masses; flesh; shell; mucus; whole animal; pearl | China; Europe; India; South America | [91,113,114,115] |
Other § | Chest and abdomen heat and pain; pain in sternum; bleeding from five aperture or subcutaneous tissue (e.g., eye; ear; nose; teeth; tongue) | 6 | 35 | Flesh; shell; pearl | China | [104] |
3.2. Supporting Evidence for the Bioactivity of Traditional Molluscan Respiratory Medicines
3.3. Taxonomic and Geographic Trends
Number of Different Mollusc Families Represented in Each Literature Type | ||||||
---|---|---|---|---|---|---|
Traditional Medicines | Biomedical Studies | |||||
TCMs * | OTMs | In Vitro | In Vivo | Clinical Trials | Model Antigen † | |
Mollusc class | ||||||
Gastropoda | 20 | 15 | 49 | 7 | 3 | 2 |
Bivalvia | 23 | 6 | 9 | 3 | 1 | 0 |
Cephalopoda | 1 | 3 | 4 | 0 | 0 | 0 |
Polyplacophora | 2 | 0 | 1 | 0 | 0 | 0 |
Aplacophora | 0 | 0 | 0 | 0 | 0 | 0 |
Monoplacophora | 0 | 0 | 0 | 0 | 0 | 0 |
Scaphopoda | 0 | 0 | 0 | 0 | 0 | 0 |
Habitat type | ||||||
Marine | 46 | 17 | 55 | 8 | 3 | 1 |
Freshwater | 0 | 3 | 2 | 0 | 0 | 0 |
Terrestrial | 0 | 4 | 5 | 2 | 1 | 1 |
4. Chemistry, Bioactivity and Biomedical Applications of Molluscan Extracts and Compounds Relevant to Respiratory Disease
4.1. Overview
Type of Study | In Vitro | In Vivo Models | Clinical Trials | Model Antigen * | Total Studies | % of Studies |
---|---|---|---|---|---|---|
No. of studies | 54 | 25 | 11 | 16 | 106 † | |
No. of compounds/extracts ‡ | 327 | 15 | 5 | 3 | ||
No. of studies reporting bioactivity § | ||||||
Anticancer | 13 | 7 | 3 | 23 | 22 | |
Antibacterial | 33 | 1 | 34 | 32 | ||
Antiviral | 4 | 4 | 4 | |||
Antifungal | 7 | 7 | 7 | |||
Anti-inflammatory ‖ | 1 | 5 | 3 | 9 | 8 | |
Antitussive | 1 | 1 | 2 | 2 | ||
Immunogenic ¶ | 2 | 15 | 4 | 16 | 37 | 35 |
4.2. Antimicrobial Activity
4.3. Anti-Inflammatory Activity
4.4. Anticancer Activity
Mollusc Class Family | Derivative Part | Specific Extract/ Compound | Microbial or Cellular Target | Effective Concentrations * | Other Important Findings | Ref |
---|---|---|---|---|---|---|
Bivalvia | ||||||
Mytilidae | Sperm | Crude perchloric acid extract (CE) and 3 isolated protamine-like (PL) proteins | Clinical and lab strains: Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae; human lymphocytes and red blood cells | MICs 7.8–250 μg/mL; MBCs (μg/mL): CE: 15.7–125, PL-II 15.7–125, PL-III 62.5–250, PIV 62.5–250 | Digested and non-digested PL-proteins had same effect; low toxicity to lymphocytes (80–90% viability), no sig. hemolysis; effect re protein membrane binding, cytosolic intrusion and nucleotide leakage | [187] |
Hemolymph (hemocytes) | Myticin C and 9 peptide fragments | P. aeruginosa, S. aureus, Micrococcus lysodeikticus | MICs >64 μM for P. aeruginosa; MIC 32 μM of 3 peptide fragments for S. aureus | [168] | ||
Hemolymph (hemocytes, plasma) | Myticin A and B peptides | M. luteus, Bacillus megaterium, S. aureus (clinical strain), Listeria monocytogenes (G+); P. aeruginosa (clinical strain), Brucella suis (G−); Fungi: Fusarium oxysporum | MBCs (μM): G+ 2.25- >20 Myt A, 1- >20 Myt B; G− >20 Myt A and B; fungi >20 Myt A, 5–10 Myt B | [167] | ||
Ostreidae | Hemolymph | Cellular (c) and acellular (a) hemolymph fractions (0.2 μm filtration) | Human adenovirus (respiratory strain AdV-5) cultured in Vero and HEp-2 cell lines | CC50 0.19–0.36 mg/mL; EC50 0.05–0.16 mg/mL | Crassostrea rhizophorae cellular fraction showed best (64%) viral inhibition, particularly w post-infection treatment; virus preincubation w both fractions protected >90% of cells indicating virucidal activity at non-cytotoxic concs | [196] |
Teredinidae | Gill (symbiotic Teredinibacter turnerae) | Tartrolon E | P. aeruginosa, methicillin-sensitive and methicillin resistant S. aureus (MSSa, MRSa) | MICs (mg/mL): 0.31 for P. aeruginosa, 0.08 for MSSa, 1.25 for MRSa | [169] | |
Cephalopoda | ||||||
Octopodidae | Suckers | Peptide (OctoPartenopin) (crude + 6 HPLC fractions + 5 synthetized fractions) | S. aureus, P. aeruginosa | MIC80 (μg/mL) 50–200 S. aureus, 50- >300 P. aeruginosa; 80 μM peptides inhibit and eradicate up to 60% biofilm formation | Also antifungal activity; improved activity with synthetized peptides | [170] |
Sepiidae † | Shell | Chitosan | Bacteria: K. pneumoniae, Bacillus cereus (G+), S. aureus, M. luteus (G−); Fungi: Aspergillus niger, Fusarium sp. | 50 mg/mL (preliminary) | S. officinalis chitosan stronger activity than shrimp and crab chitosan; ZIs similar to gentamycine for G−, > cyclohemimide for fungi | [135] |
Shell | Chitosan | Streptococcus pneumoniae, S. aureus (G+), P. aeruginosa, K. pneumoniae (G−) | MIC (μg/mL): 60–100 (G−), 100 (G+) | Higher MICs for phosphorylated chitosan | [136] | |
Salivary glands | PSG toxin (glycopeptide) | K. pnemoniae, Streptococcus pyogenes | 1–50 μM (preliminary) | Little difference between 1–50 μM concs; low toxicity to zebrafish embryo | [290] | |
PSG toxin (glycopeptide) | K. pnemoniae, S. aureus, P. aeruginosa | 25–100% (preliminary) | Susceptibility: S. aureus > K. pneumonia > P. aeruginosa; ZIs comparable to Ciprofloxacin | [291] | ||
Sepiidae, Octopodidae | Body | Crude CH3OH extracts | Clinical bacterial strains: P. aeruginosa, K. pnemoniae, S. aureus, S. pneumoniae, Streptococcus sp., Vibrio alginolyticus; Fungi: Pencillium italicum, Alternaria alternata (allergen), Fusarium equisetii | MIC range 60–100 mg/mL | Extract from S. kobiensis showed the best/broadest spectrum activity; no positive control or toxicity data | [185] |
Gastropoda | ||||||
Achatinidae | Mucus | Mytimycin-AF (antimicrobial peptide) | S. aureus, B. megaterium, K. pneumoniae | MIC (μg/mL) S. aureus 1.9, B. megaterium 15, K. pneumoniae 30 | Better activity than human AMP control for S. aureus; minimal hemolysis (max 3.9% at 329 μg/mL) | [292] |
Achatinidae, Helicidae | Mucus | Crude mucus and 4 size-separated fractions | K. pneumoniae, P. aeruginosa (3 strains), S. aureus, S. pyogenes, Acinetobacter sp. (clinical), Serratia marcescens (clinical) | 1:3 crude mucus:PBS (preliminary) | Crude H. aspera mucus inhibited S. aureus and P. aeruginosa; A. fulica mucus inhibited S. aureus; other microorganisms unsusceptible | [174] |
Babyloniidae | Body | Crude extracts ‡ | P. aeruginosa, K. pneumoniae, S. aureus, S. pneumoniae; Fungi: A. flavus | Crude extract (preliminary) | Ethanol extract had highest antimicrobial activity; most effective against P. aeruginosa, least effective against S. aureus | [175] |
Clathurellidae | Hepatopancreas (symbiotic Streptomyces sp.) | CH3OH extract (lobophorin compounds) | Mycobacterium tuberculosis, P. aeruginosa, Burkholderia cepacia; CEM-TART cell line | MIC90: 1.3–24 μM for M. tuberculosis, >100 for P. aeruginosa and B. cepacia | Strong cytotoxicity at similar MIC concentrations (0.3–100 μM) therefore not a suitable therapeutic candidate | [117] |
Conidae | Venom | Conotoxin MVIIA and 9 analogues | S. aureus | MICs: >500 μM MVIIA, 7–78 μM analogues | MVIIA considered inactive, different activity among analogues re. cyclic structure and side chain modification | [293] |
Cypraeidae ‖ | Shell | Powder | Micrococcus sp. | 4–5% w/v shell powder in distilled water (preliminary) | Dose-dependent antipyretic effect in vivo (not sig) | [134] |
Dorididae | Sperm (also in egg masses) | 5’-deoxy-5’-methylthio-adenosine (MTA) and two natural analogues (xylo-MTA and xylo-A) | S. aureus, Corynebacterium diphtheriae; Vero and C8166 cell line | MICs: MTA 33 μM, xylo-MTA 200 μM, xylo-A 18 μM | MICs always higher than minimum non-toxic concentrations; xylo-A most toxic, xylo-MTA least toxic; no positive control | [172] |
Fissurellidae | Body | Scutinin A and B | P. aeruginosa | MIC: 30 μg/mL scutinin A, 100 μg/mL scutinin B | [171] | |
Helicidae, Muricidae | Hemolymph | Experimentally purified Hc (βc-HaH subunit + 8 FUs, RvH1 + 4 FUs) | S. aureus, S. pyogenes, P. aeruginosa | MIC: 6.5 μM βc-HaH; MIC not calculated for RvH1 (1.25–10 μM range) | HaH more effective than RvH; native Hc more effective than subunits from both species; βc-HaH S. aureus and S. pyogenes 60 and 51% inhibition respectively, RvH1 35% inhibition, relative to control; limited activity against P. aeruginosa | [73] |
Muricidae | Hemolymph | Experimentally purified Hc (RvH), glycosylated (RvH-c) and non-glycosylated (RvH-b) subunits | Respiratory synctial virus (RSV), cultured in Hep-2 cell line | RvH-c 1 mg/mL | RvH-c effective against replication of RSV (71.4% inhibition at 1 mg/mL), no effect on other tested viruses (poliovirus, cocksackie virus); native RvH and RvH-b no antiviral activity; no cytotoxic effect at highest concs | [197] |
Egg masses | Crude extracts (de, eth, CHCl3, CH3OH-H2O) # and isolated ty, tv, Tp, 6-b § | P. aeruginosa (G−), S.aureus (G+) | MICs (mg/mL): 0.0005 tv, 0.5–1.0 ty, 0.1–1.0 6-b, >1 Tp, 1.0–10 CHCl3, 0.1 de, 10 eth, >50 CH3OH-H2O | Lipophilic extracts had better activity; tv bacteriostatic, ty bactericidal | [149] | |
Hemolymph | Experimentally purified Hc (11 protein fractions) | S. aureus, K. pneumoniae | 113–598 μg/mL | Peptides 8, 9, 10 and 11 showed >90% inhibition; S. aureus more susceptible; different proteins more/less active against different bacteria; longer protein chains more effective | [294] | |
Body | Crude extracts ** | K. pneumoniae, P. aeruginosa, S. pneumoniae, Citrobacter sp., B. cereus | MICs 0.05–0.12 mg | Acetone extract most effective; similar effectiveness against other (non-resp) pathogens | [184] | |
Olividae | Body | Acid-acetone peptide extract | S. aureus, P. aeruginosa, K. pneumoniae | MIC (mg/mL): 2.5 S. aureus, 0.039 P. aeruginosa, 1.25 K. pneumoniae; MBC (mg/mL): 2.5 S. aureus, 1.25 P. aeruginosa, >2.5 K. pneumoniae | Protein ZIs comparable to control antibiotics; ciprofloxacin and cefotaxime MICs reduced by >100% w protein extract, metronidazole and erythromycin MICs increased; effects re changes in membrane porosity/permeability | [179] |
Body | Acid-acetone peptide extract | P. aeruginosa | MIC: 39.06 ug/mL (Gentamycin MIC 1.95 ug/mL) | Bacteriostatic; dose dependent reduction in virulence factors (pyoverdine, pyocyanin, protease)- peptide mix (69%) similar to gentamycin (72%) at 1/2 MIC; 50% reduction in biofilm formation at 39 ug/mL, 2.5 mg/mL required to degrade pre-formed biofilm | [178] | |
Onchidiidae | Body | Dolabellanin B2 (AMP) | S. aureus, P. aeruginosa, K. pneumoniae | MICs: 10–25 ug/mL | Structure-function characterization; better activity against G+; compound identified as one previously isolated from Dolabella auricularia | [295] |
Patellidae, Donacidae †† | Body | Acid-acetone extract | S. aureus, S. pneumoniae, K. pneumoniae, P. aeruginosa | MICs 17–20 mg/mL | ZI’s similar to ciprofloxacin; Galeta paradoxa extract stronger antibacterial than Patella rustica extract, which showed good antifungal activity | [296] |
Pharidae | Body ‡‡ | 2 sialic acid-binding lectin recombinant proteins (rSgSABL-1, -2) | Staphylococcus aureus, Micrococcus luteus; Solen grandis (mollusc) hemocytes; mice (n = NA) immunised i.p. 2x w rSgSABL-1 (100 μg/mL) or rSgSABL-2 (180 μg/mL) in CFA ‖‖ | 100 μg/mL (phagocytosis), 90 μg/mL (microbe agglutination, and encapsulation); 100–180 μg/mL (Ab production) | High binding affinity to S. aureus peptidoglycan (PAMP) (also LPS, β-glucan); agglutination effect on M. luteus; enhanced phagocytosis and encapsulation ability (p < 0.05); antisera Ab reactivity with rSgSABL-1 and -2 | [188] |
Plakobranchidae | Body | Kahalalide F and 8 analogues | Bacteria: P. aeruginosa, methicillin resistant S. aureus, M. tuberculosis (H37Rv), M. intracellulare; Fungi: Cryptococcus neoformans, A. fumigatus, Fusarium sp. | MIC 9.4–>16 μg/mL Kahalalide F analogues (M. tuberculosis); 30 μM antifungal | >90% inhibition of M. tuberculosis and up to 100% fungicidal activity comparable to controls; no activity against P. aeruginosa or S. aureus; high test concs- cytotoxicity test concs lower than MICs | [253] |
Body | Kahalalide F, analogues KZ1 and KZ2 | Aspergillus sp., Fusarium sp. | 20 mg KZ1 and KZ2 | Analogue bioactivity profiles comparable to KF; antifungal activity comparable to ketonazole | [257] | |
Strombidae | Body | Crude extracts ## | S. aureus, P. aeruginosa | 1–100 μg/mL H2O extract (preliminary) | Stronger activity against P. aeruginosa over S. aureus | [297] |
Truncatellidae | Body (symbiotic Streptomyces sp.) | 7,8-dideoxygriseorhodin C (DC) | Methicillin-resistant S. aureus; MDCK and AA8 cell lines | MICs (μg/mL): 0.08–0.12 DC, 1.59–6.24 oxacillin; combination DC 0.01–0.02 DC and 0.02–0.298 Oxacillin | DC stronger than oxacillin as single agents; reduction MICs w combination; no cytotoxicity (IC50 15.84 μg/mL and >49.5 μg/mL for MDCK and AA8 cells, respectively) | [176] |
Veronicellidae | Mucus | Concentrated crude mucus and 4 fractions (PUFA 39, 40, 49, 50) | Measles virus (Edmonston wild-type), cultured in Vero cell line | 60–220 ng/mL mucus/fraction 39 inhibition of viral replication; 2% mucus/fraction 39 inhibition of CPE | Effect attributed to disruption of the virus’ lipoprotein envelope; not cytotoxic to Vero cells (IC50 41 μL crude, 92.6 μL fraction 39) | [154] |
Mucus | Crude concentrated mucus and 3 fractions (PUFAs 39, 40, 49) | Influenza A (H1N1) virus, cultured in MDCK cell line | 2% or 60–80 ng/mL crude mucus and fraction 39 | Inhibition of viral replication and >80% decrease in viral load in infected cells w crude mucus and frac 39; not cytotoxic (although IC50 NA); may interfere w binding of virus to host cell receptor | [153] | |
23 families §§ | Egg masses | Crude homogenised egg material and extracts ††† | P. aeruginosa, S. aureus | 1–10 mg/mL CHCl3 and CH3OH-H2O extracts (preliminary) | S. aureus and P. aeruginosa inhibited by 79% and 72% of tested egg masses, respectively; no dif in activity between tough and gelatinous egg masses | [65] |
16 families *** | Body | CHCl3 extracts | Bacteria: S. aureus, P. aeruginosa, K. pneumoniae; Fungi: A. fumigatus; chicken red blood cells and brine shrimp | Crude extracts (preliminary) | Positive antimicrobial activity; best result w extract of Conus betulinus; low toxicity to brine shrimp (LC50 12–42 μg/mL); 10/25 sp. extracts showed hemolytic activity; no antibiotic controls | [298] |
5 families ‡‡‡ | Body, gill and mantle (GM), digestive gland (DG) | 10, 40 and 80% SPE fractions of acidic (HCl) extract in sterile water | M. luteus and B. megaterium; Vero cell line | Most effective MICs (μg/mL): 43 80% DG extract both bacteria, 63 80% DG extract M. luteus, 40 80% G+M extract B. megaterium, 2560 M. luteus) | 40 and 80% fractions from all sp. effective; Crassostrea edule extracts showed best activity (also against non resp viruses); <50% cytotoxicity; positive controls (lysozyme and polymyxine B) more effective than extracts | [45] |
Mollusc Class Family | Derivative Part | Specific Extract/ Compound | Microbial or Cellular Target | Effective Concentrations | Other Important Findings | Ref |
---|---|---|---|---|---|---|
Bivalvia | ||||||
Mactridae * | Body | Spisulosine | SW1573 (human alveolar carcinoma) cell line (and 4 other human tumor cell lines) | GI50: 1.3 μM | Spisulosine most effective of tested compounds- >positive controls Cisplatin (3.0 μM) and Etoposide (15.0 μM); GI50′s 0.7–2.6 μM for range of cell lines- SW1573 intermediate sensitivity; selective CK1ε inhibition | [299] |
Ostreidae | Hemolymph (hemocytes) | Tumor necrosis factor (CgTNF-2) | A549 (human alveolar carcinoma) | 200 ng/mL recombinant CgTNF-2 | CgTNF-2 expression upregulated in response to bacterial PAMPs (incl. Staphylococcus aureus), and serum lysosome activity, NO content and antibacterial activity (non-resp) increased (p < 0.05) | [247] |
Veneridae | Body | (NH4)2SO4 fractionated peptide (‘Mere15′) | A549 and range of other non-respiratory cancer cell lines (breast, cervical, colorectal, pancreatic, liver); benign cells NIH 3T3 and MCF-10A | IC50: 31.8 μg/mL | A549 most susceptible among cancer types, therefore used in subsequent assays and animal model; not cytotoxic to benign cells (IC50 > 120 μg/mL) | [252] |
Cephalopoda | ||||||
Loliginidae † | Digestive gland/liver | Lipid extract | A549 and Vero cell lines | 70% growth inhibition at 960 μL/mL, 55% at 480 μL/mL; CC50 260 μg/mL for A549 (NA for Vero) | Better growth inhibition of A549 (max 70%) compared to Vero (max 7%) | [249] |
Gastropoda | ||||||
Ampullariidae | Body | “Polysaccharide extract” ‡ | A549 cell line | 20–200 μg/mL | 24-h reduction in tumor growth: 31% at 20 mg/mL, 43% at 50 mg/mL, 46%, at 100mg/mL, 57% at 200 μg/mL; 84% antioxidant at 5 mg/mL | [250] |
Aplysiidae | Body | Dolastatin-10 | Human SCLC cell lines (NCI-H69, NCI-H82, NCI-H446, NCI-H510) | IC50 range 0.03–0.184 nM | >50% G2/M phase arrest, bcl-2 phosphorylation; pro-apoptotic mechanism | [254] |
Chilondontidae | Body | Crude CHCl3 extract (1.25%) in Hanks Balanced Solution | A549 cell line | 5–20 μg/mL | 30–40% cytotoxicity at 5–20 μg/mL; apoptosis at 10 μg/mL, not increasing w higher doses or exposure time; wound area reduced by 28.3% at 5 μg/mL; all results p < 0.05; inhibitory effect on matrix metalloproteinase | [248] |
Helicidae | Mucus | Helicidine formula (glycoproteins) (purified NaCl extract) | Tracheas dissected from Dunkin-Hartley guinea pigs; epithelium (E+) and epithelium-free (E−) strips prepared | 0.005–0.5 mg/mL (min-max effective) | Dose dependent reduction of contraction by 35% in E+ and 25% in E−; PGE2 higher post treatment (p < 0.01); related to COX inhibition (p < 0.01) | [79] |
Hemolymph | Experimentally purified Hc (HpH) | Influenza (H3N2) immunisation model using Balb/c mice (n = 5–8/group) immunised w 50 μg influenza peptide (IP), IP w CFA, IP w alum, or IP w HpH (16, 40, 100 μg) | 100 μg HpH; 50 μg antigen + 100 μg HpH | Ex vivo spleenocytes of mice treated w IP+100 μg HpH showed stronger cytotoxicity against infected cells in vitro compared to all other groups (p < 0.0005) | [83] | |
Plakobranchid-ae | Body | Kahalalide F (KF) and 8 analogues | A549 and NCI-H322M (human bronchioalveolar carcinoma) and Vero cell lines | GI50: 0.131–13.7 μM (compound-tumor specific e.g., for A549 analogues 8 and 16 IC50 0.166 and 13.189 μM, 0.165 and 0.167 µM for NCI-H322M) | Some compounds showed higher potency than Paclitaxel; similar anticancer activity among other tested cancer cell lines; no cytotoxicity at 4.76 μg/mL | [253] |
Body (originally) | KF (synthetic) | 4x human NSCLC cell lines (A549, SW1573, NCI-H292 and NCI-H460) | IC50 0.1–7.0 μM | A549 and H292 particularly sensitive, H460 least sensitive; inhibition of ErbB andPI3K-Akt signaling at IC50 concs and necrosis-like cell death | [256] | |
Body (originally) | PM02734 (elisidepsin trifluoroacetate; synthetic KF3 derivative) | HOP62 (human lung adenocarcinoma), A549 (human alveolar carcinoma), DV90 (human metastatic pleural carcinoma) cell lines | Elisidepsin IC50 ~4 μM for HOP62, <0.25 μM for A549, ~0.3 μM for DV90 | Downregulation of ErbB3, Akt and MAPK pathways in all cell lines; synergistic/additive effects w other cisplatin, paclitaxel and gemcitabine in all cell lines- combination therapy to improve clinical efficiency | [258] | |
Body (originally) | PM02734 (elisidepsin trifluoroacetate; synthetic KF3 derivative) | 8 x human NSCLC cell lines (H322, A549, H661, H1299, H1975, H358, H460, H1650) | IC50 0.3 μM to >5 μM (0.58 μM for A549) | All cell lines sensitive to PM02734, only 2 cell lines sensitive to erlotinib; positive correlation between ErbB expression and sensitivity to PM02734; erlotinib inhibited EGFR, AKT and ERK1/2 phosphorylation whereas PM02734 strongly inhibited phosphorylation of ErbB3 and AKT and, to a lower extent, EGFR and ERK1/2 hence the efficacy of combined treatment in vivo | [263] | |
Mucus (and body) | KF, analogues KZ1 and KZ2, crude CHCl3-CH3OH extract | A549 (and other non-respiratory cancer) cell lines | A549 IC50: 1 μM KZ1, 3 μM KZ2, 1 μM | Analogue bioactivity comparable to KF; low IC50 values for lung cancer relative to other tested cancer cell lines; mucus extracts stronger | [257] | |
7 families ‖ | Body | 95% C2H5OH extract | A549 cell line; mouse spleenocytes | 0.25–1 mg/mL | 73–96% tumor growth inhibition at 1 mg/mL, 63–89% at 0.25 mg/mL; molluscan extracts showed stronger anti-tumor properties than other invertebrate extracts and had strong promotion activity on T and B lymphocytes (+25% at 1 μg/mL); low toxicity (not quantified) | [251] |
Mollusc Class Family | Derivative Part | Specific Extract/ Compound | Model Design * | Main Findings | Effective Concentrations | Ref |
---|---|---|---|---|---|---|
Bivalvia | ||||||
Mytilidae | Body | Lipid extract (‘Lyprinol’) | Murine model of allergic airway disease using Balb/c mice (n = 3–8/group) fed a low-fat background diet treated w 200 uL Lyprinol (or fish oil control) p.o daily, 14 d prior to challenge w i.n. OVA (10 mg in 0.9% saline) (or PBS alone) on days 12–15 | Lyprinol group had lower eosinophil counts and fewer mucus-secreting cells (p < 0.05), other inflammatory cells lower (not sig); no sig dif. in Ab levels between fish oil and Lyprinol; lower IL-13, higher IL-4 and IFN-y in Lyprinol group (p < 0.05); both fish oil and Lyprinol suppressed airway resistance (p < 0.05); Lyprinol efficacy suggested re. synergistic effects between multiple nutritional components/PUFA profile | 200 μL | [208] |
Pectinidae | Body | Protease extracted polysaccaride heparin sulfate analog (HS) | Lung metastasis model using mice (n = 9) treated w 8 mg/kg HS i.v. (or mammalian heparin or chondroitin controls) 10 min before challenge w i.v. Lewis lung carcinoma cells; separate model of P-selectin-mediated tumor cell-platelet association using labelled LLC cells w or w/out pre-treatment w 200 μg HS † | Molluscan HS inhibited lung metastasis (10 foci/lung control vs. 1 foci/lung HS; p < 0.05) w markedly smaller tumor size, and reduced heparinase activity (p < 0.05); reduced tumor–platelet complex to 30% (control 70%); similar effect to mammalian heparin at lower molar concentration; blocks both P-selectin-mediated interactions and heparinase activity blunting metastasis and inflammation | 8 mg/kg | [274] |
Pharidae | Body ‡ | 2 sialic acid-binding lectin recombinant proteins (rSgSABL-1, -2) | Non-specific pathogen immunisation model using mice (n = NA) immunised i.p. 2x w rSgSABL-1 (100 μg/mL) or rSgSABL-2 (180 μg/mL) in CFA | Antisera antibodies reactive with rSgSABL-1 and -2 in Western Blot Analysis; strong Staphylococcus aureus peptidoglycan (PAMP) binding affinity (p < 0.05 compared to PBS and pre-serum) | 100–180 μg/mL | [188] |
Veneridae | Body | (NH4)2SO4 fractionated peptide (‘Mere15′) | Human lung cancer (A549) xenograft model using Balb/c mice (n = 6/group) immunised s.c. w Mere15 12.5, 25.0 or 50.0 mg/kg (or cyclophosphamide [CTX] 50 mg/kg or normal saline) each day for 10 d | Mere15 at 25 and 50 mg/kg doses displayed 51% and 69% growth inhibition (p < 0.01), respectively; comparable to (though not sig dif than) CTX causing 53% inhibition; A549 most susceptible among cancer types in vitro therefore used in subsequent assays and animal model | 25–50 mg/kg | [252] |
Gastropoda | ||||||
Aplysiidae | Body | Dolastatin-10 | Human small cell lung cancer (SCLC) (NCI-H446) xenograft model using CB-17 SCID mice (n = 8–10/group) treated w 450 μg/kg dolastatin 10 i.v. 26 and 36 d (or 7 and 17 d) after tumor inoculation | Treatments at 7 and 17 d completely inhibited tumor formation and increased survival (median 59 d control, >214 d treatment); treatments at 26 and 36 d (after tumor formation) caused tumor shrinkage (mass 1635 mg control, 44 mg treatment), growth delay, and increased survival (median 42 control, 91 treatment); pro-apoptotic mechanism | 450 μg/kg | [254] |
Body | TZT-1027, (dolastatin 10 derivative) | Human LX-1 lung carcinoma xenograft model using Balb/c mice treated w 0.5, 1 and 2 mg/kg TZT-1027 (and Cisplatin- 5 and 10 mg/kg) administered i.v. after tumor established at 7 d, or both 7 and 14 d ‖ | 1–2 treatments caused tumor regression of 84–98% at 1 mg/kg, 99% at 2 mg/kg (> cisplatin: 49–52% at 5 mg/kg, 83% at 10 mg/kg); greater regression of lung cancer compared to breast cancer; 10% and 80% de-polymerisation of microtubule proteins 10% at 1.0 μM, 80% at 10 μM | 1–2 mg/kg | [255] | |
Limacidae | Body | Aqueous Limax extract in MEM | COPD model using C57BL/6J mice (n = 8/group) treated w A) normal air + 2.18 g/kg extract; B) cigarette smoke (CS) + purified water; C) CS + 2.18 g/kg extract; CS = 9 cigarettes/h, 4 h per d, 6 d per wk in whole body exposure chamber for 90 d; extract given i.g. 0.5 h before daily CS exposure; cytotoxicity assay 0.01 μg/mL–10 mg/mL extract | CS-exposed Limax-treated mice improved pulmonary function compared to untreated mice (p < 0.05); less visual symptoms (e.g., weakness, wheezing), reduced lung damage, hyperplasia, inflammation, alveolar intercept and airway thickness (p < 0.01); reduced BALF inflammatory cell count (p < 0.01), inflammatory cytokines (p = 0.01–0.05) and Muc5AC secretion/expression (p < 0.01); suppression of inflammatory signaling cascades (p < 0.05); no sig cytotoxicity at effective doses; PPAR-γ enhancement and P38 MAPK pathway suppression | 2.18 g/kg | [78] |
Body | Limax lyophilized powder H2O suspension | Allergic asthma model using guinea pigs (n = 15/group); sensitization using AlOH2 and egg albumin, treated w Limax (189, 63, 21 mg/kg/d) (or Aminophylline 80 mg/kg/d control); inhalation challenge after 7 d | Reduced asthma onset time, mortality, inflammatory markers (BALF/peripheral blood leukocyte count, eosinophil infiltration, IL-2 and IL-4) (p < 0.05); 63 mg/kg more effective than Aminophylline at reducing onset time (p < 0.05) | 63 mg/kg | [140] ¶ | |
Body | Limax powder in H2O | Lewis lung carcinoma model using mice (n = 10/group); treatments 800–2500 mg/kg | Inhibitory effect on tumor growth (47% inhibition at 800 mg/kg) and prolonged survival (p < 0.01) | 800 mg/kg | [111] # | |
Muricidae | Hypobranchial gland (HBG) | Crude CHCl3-CH3OH extracts, 6-bromoisatin | Acute lung injury/inflammation model using C57Black/6 mice (n = 5–6/group) treated w HBG extract (0.5 or 0.1 mg/g), or 6-bromoisatin (0.05 or 0.1 mg/g) in 100 μL grape seed carrier oil (or PBS/carrier controls) administered p.o. 48 h, 24 h and 1 h prior to challenge w i.n. LPS (E. coli-derived) (1.25 mg/kg in 50 μL PBS) | Lower BALF total cells, neutrophils, TFN-α, IL-1β, and total protein in all treatments (p < 0.0001); 6-bromoisatin generally stronger effect (and lower concs used) but no sig difference between treatments; all doses of each compound significantly minimised all indicators of acute inflammatory damage to the lungs (p < 0.0001); positive correlation between histopathological scores and inflammatory markers (particularly TNF-α, IL-1β and neutrophils) in BALF (R2 0.53–0.77, p < 0.0001) | 0.5–0.1 mg/g HBG extract; 0.05–0.1 mg/g 6-bromoisatin | [77] |
Muricidae **, Helicidae | Hemolymph | Experimentally purified Hc (RvH or HpH) | Colon cancer (C-26) model measuring lung metastasis in Balb/c mice (n = 20/group) sensitised i.p. w 200 μg RvH or HpH 2 wks before tumor inoculation and 100 μg weekly i.t.t. after solid tumor formation (sensitised) or 100 μg weekly i.t.t. only (non-sensitised); controls: PBS+challenge, RvH/HpH only no challenge | Lower surface lung metastases count in sens RvH, sens HpH and non-sens HpH groups; no sig dif. in cytokine profiles between groups; >anti-C-26 antibodies (p < 0.05); higher % survival in sens groups; >body weight in unsens groups (p = 0.001-0.05); reduced C-26 tumor size (p < 0.01) although all developed small tumors; HpH/RvH control survival NA | 100 μg (w/w-out 200 μg dose pre-tumor formation) | [76] |
Plakobranchid-ae | Mucus (originally) | PM02734 (Elisidepsin- synthetic KF3 derivative) | NSCLC (A549) model using NUR-NU-F-M mice (n = 5–7/group) treated w PM02734 (0.1 mg/kg × 3/wk for 2 wk i.v.), Erlotinib (50 mg/kg × 5/wk for 2 wks p.o.), combination (PM02734 i.v. 0.1 mg/kg × 3/wk for 2 wks i.v + Erlotinib p.o. 50 mg/kg × 5/wk for 2 wks p.o.), or no treatment; in vitro component used PM02734 0–10 uM | Combination treatment enhanced survival (>150 d) compared to PM02734 (54 d), Erlotinib (39) and control (23) (p = 0.0003–0.002); Erlotinib inhibited EGFR, AKT and ERK1/2 phosphorylation in vitro whereas PM02734 inhibited phosphorylation of ErbB3 and AKT and, to a lower extent, EGFR and ERK1/2 hence the efficacy of combined treatment | PM02734 0.1 mg/kg w or w/out 50 mg/kg Erlotinib | [263] |
Mollusc Class Family | Derivative Part | Specific Extract/ Compound | Study Type and Design * | Main Findings | Effective Concentrations | Ref |
---|---|---|---|---|---|---|
Gastropoda | ||||||
Helicidae | Mucus | Helicidine | Double-bind, placebo-controlled, parallel-group clinical trial involving 30 COPD patients w history of chronic bronchitis and stabilised nocturnal cough (>20 cough episodes/night) treated w 2x 15-mL doses of 10% helicidine syrup (or placebo syrup) p.o. 3x daily for 3 d over 5-d observation period | Frequency of cough episodes/night reduced: 4.7–5.1 pre-treatment, 2.7–4.9 placebo, 1.3 helicidine group (p < 0.05); duration of cough period (during sleep and awakening) also reduced (p < 0.05); no sig difference between subjective endpoints (Spiegel questionnaire, CGI) | 15-mL 10% | [80] |
Plakobranchidae | Body (originally) | Kahalalide F (KF) | Phase I clinical trial and pharmacokinetic study involving 38 cancer patients (13 w lung cancer) administered i.v. 50 μg/mL kahalalide F weekly starting at 266 μg/m2 increasing between 25–100% over 21–109 cycles | Tumor shrinkage by 25–50% or stable disease in lung cancer patients; mild-moderate side effects w severe blood transaminase activity being the dose-limiting factor (3 cases); 650 μg/m2 recommended for future studies | 650 μg/m2 | [260] |
Body (originally) | KF | Non-randomised, multi-centre phase II clinical trial of KF as a second line therapy in 31 patients w advanced non-small cell lung cancer (NSCLC) administered i.v. 650 μg/m2 for 1 h/wk | One partial response observed; stable disease reported in 8 patients; majority of clinical benefit seen in patients with squamous cell carcinoma | 650 μg/m2 | [261,262] | |
Body (originally) | PM02734 (Elisidepsin- synthetic KF3 derivative) | Phase 1 clinical trial and pharmacokinetic study involving 42 cancer patients (16 w lung cancer) administered i.v. 0.5 mg/m2 escalated at 100% increments (depending on grade of toxicity; median 2 cycles/patient, 3.2 mg/wk) | Disease stabilization in 12 patients (none w lung cancer), 1 patient (with metastatic esophageal adenocarcinoma) complete response; mild-moderate grade toxicities in ~17% of patients, grade 3 toxicities (hematologic, biochemical [transaminase]) in ~15% of patients lasting 7–14 d; necrosis-like cell-death | Max tolerable dose: 6.8 mg/m2 | [259] | |
Bivalvia | ||||||
Mytilidae | Body | Lipid extract (‘Lyprinol’) | Double blind, randomised placebo-controlled parallel-group clinical trial involving 23 atopic asthma (mild-mod) patients (and 23 healthy subjects) treated w 2x 150 mg Lyprinol (or olive oil) capsules p.o. 2x daily for 8 weeks | Mean daytime wheeze and exhaled H2O2 sig reduced and morning PEF sig higher w Lyprinol treatment (p < 0.05); no differences in night awakenings and use of short-acting B2 agonist meds; inhibition of 5’-lipoxygenase and cyclo-oxygenase pathways responsible for production of eicosanoids | 150 mg Lyprinol (50 mg extract in 100 mg olive oil) | [210] |
Body | Lipid extract (‘Lyprinol’) | Double blind, randomised placebo-controlled clinical trial using 73 (71 completed) children aged 6–13yrs treated w 2x 150 mg Lyprinol (or olive oil) capsules p.o. 2x daily for 7 months | Reduction in Fluticasone use (< 57.8 μg/d vs. 42.8 μg/d; p = 0.27), rescue β-agonist use (42.6% vs. 53.8%; p = 0.67); fewer asthma exacerbations (annualised rate of exacerbation 0.5 Lyprinol vs. 0.86 control); higher % reporting little/no trouble w their asthma (97 vs. 76%; p = 0.057); many other clinically important though non-significant improvements | 150 mg Lyprinol (50 mg extract in 100 mg olive oil) | [209] | |
Body | Lipid extract PCSO-524 (‘Lyprinol/OmegaXL’) | Double blind, randomised placebo-controlled clinical trial involving 20 patients w asthma and hyperpnea-induced bronchoconstriction treated w 8x 150 mg Lyprinol capsules p.o. daily for 8 weeks, followed by 2 weeks washout phase (usual diet) followed by 3-week special PCSO-524 diet phase (or usual diet control) | After the final phase, Lyprinol treatment and specific diet caused reduction in bronchodilator use and increase in mean morning and evening PEF (p < 0.05); no sif dif. in asthma symptom scores or FEV1; lower expired breath NO and urinary markers (p < 0.05) | 150 mg Lyprinol (50 mg extract in 100 mg olive oil) | [207] |
5. Molluscan Hemocyanins as Therapeutic Adjuvants and Model Antigens
6. Sustainable Supply and Traditional Knowledge Considerations
7. Conclusions: Promising Molluscan Extracts and Compounds for the Treatment and Prevention of Respiratory Disease
- This review highlights that there is a paucity of research on the bioactivity of molluscan extracts and compounds, considering the high diversity of species in this phylum and their merit as traditional medicines. Here, we have demonstrated the links between the anti-inflammatory, antimicrobial, anticancer, and immunomodulatory activity of molluscan extracts and compounds and their therapeutic potential in the prevention and treatment of respiratory diseases.
- At least 100 traditional medicines incorporating over 300 species of Mollusca have been used to treat respiratory diseases for thousands of years. Most of these are yet to receive research attention, and those few that have shown interesting bioactivities that validate some applications. There is a continued need to develop an evidence base toward the integration of quality-controlled traditional medicines.
- We identified particular incentive for biomedical research that elucidates anti-inflammatory factors from mollusc species/families comprising traditional medicines as there is likely to be some chemical basis consistent with their extensive use for alleviating inflammatory symptoms. Shell extracts are widely used but understudied and worthy of further investigation, as are certain taxonomic classes and families used in traditional medicines. The Polyplacophora and Scaphopoda, a wider range of Bivalvia including Veneridae, and shelled Gastropoda including Muricidae are of interest. Respiratory disease-focused ethnomedical studies would also be useful.
- Based on biomedical data, we expect that studies using molluscan compounds isolated from specialized glands, reproductive organs, microbial symbionts, and hemolymph would prove worthwhile.
- The exploration of novel molluscan Hcs holds good potential for the discovery of new antiviral and immunomodulatory agents, and therapeutic alternatives to KLH. Hcs could be tested in combination with other antiviral factors (e.g., zinc) from the same mollusc. Snail mucus should also be further investigated for anti-spasmodic, anti-inflammatory and anti-viral activities.
- Molluscan compounds may be valuable in the treatment of biofilm-associated respiratory infection and improve the efficacy of antibiotics. Further biofilm inhibition/disruption studies are needed and should be inclusive of S. pneumoniae and P. aeruginosa.
- Derivatives of KF and dolastatin 10 are the most potent molluscan anticancer compounds and of continued interest. Several compounds show anticancer activity and need to be tested against respiratory cancers (e.g., brominated indole/isatin derivatives; others in [66] and structural modifications). In vivo models of various cancer types should include measures of lung metastases and cytotoxicity to healthy cells.
- Compounds with bioactivities relevant to a range of respiratory diseases (e.g., anti-inflammatory activity) should be further explored, as well as combinations of compounds (molluscan-molluscan and molluscan-standard agents) to improve treatment efficacy for a single disease and address issues of chemotherapeutic and antimicrobial resistance.
- Overall, there is a need for more targeted research based on specific hypotheses related to respiratory disease using extracts and compounds derived from molluscs, with consideration to the sustainability of supply and attribution of traditional knowledge.
Supplementary Materials
Funding
Acknowledgments
Conflicts of Interest
Common Abbreviations
TCMs | traditional Chinese medicines |
OTMs | other traditional medicines |
Hc | Hemocyanin |
COPD | chronic obstructive pulmonary disease |
ARDS | acute respiratory distress syndrome |
NSAIDs | non-steroidal anti-inflammatory drugs |
MIC/MBC | minimum inhibitory/bactericidal concentration |
IC50/GI50/CC50 | concentration causing 50% inhibition/growth inhibition/cytotoxicity |
PUFAs | polyunsaturated fatty acids |
FDA | United States Food and Drug Administration |
Abs | antibodies |
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Summer, K.; Browne, J.; Liu, L.; Benkendorff, K. Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease. Mar. Drugs 2020, 18, 570. https://doi.org/10.3390/md18110570
Summer K, Browne J, Liu L, Benkendorff K. Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease. Marine Drugs. 2020; 18(11):570. https://doi.org/10.3390/md18110570
Chicago/Turabian StyleSummer, Kate, Jessica Browne, Lei Liu, and Kirsten Benkendorff. 2020. "Molluscan Compounds Provide Drug Leads for the Treatment and Prevention of Respiratory Disease" Marine Drugs 18, no. 11: 570. https://doi.org/10.3390/md18110570