|Year : 2019 | Volume
| Issue : 12 | Page : 3798-3807
Pharmacological and biochemical properties of Zingiber zerumbet (L.) Roscoe ex Sm. and its therapeutic efficacy on osteoarthritis of knee
Hassan Kiani Ahmadabadi1, Mohammad Reza Vaez-Mahdavi2, Mohammad Kamalinejad3, Seyed Shamsa Shariatpanahi4, Tooba Ghazanfari5, Farhad Jafari6
1 Department of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
2 Department of Physiology, School of Medicine, Shahed University, Tehran, Iran
3 School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Internal Medicine, Mostafa Khomeini Hospital, Shahed University of Medical Sciences, Tehran, Iran
5 Immunoregulation Research Center, Shahed University, Tehran, Iran
6 Department of Health and Social Medicine, Shahed University, Tehran, Iran
|Date of Submission||28-Jul-2019|
|Date of Decision||21-Aug-2019|
|Date of Acceptance||18-Oct-2019|
|Date of Web Publication||10-Dec-2019|
Dr. Mohammad Reza Vaez-Mahdavi
Department of Physiology, School of Medicine, Shahed University, Tehran
Source of Support: None, Conflict of Interest: None
Osteoarthritis (OA) as the most frequent form of knee arthritis is one of the most annoying complications amongst old peoples. There are different pharmacological and non-pharmacological remedies which could be applied for treatment of knee OA. It's while, significant side effects mostly in patients who are older are the dangerous limiting factors. Integrative, supplementary, traditional remedies have been applied from long time ago in treatment of such chronic diseases like OA. Various topical and oral remedies have been presented in treatment of OA worldwide. In spite of the fact there are multiple remedies for reduction symptoms of patients who suffer from disorders and related inabilities which could enhance their life quality. Remedies which have been applied for a long time for treatment of OA have newly discovered to induce injury to some patients. On the other side, additional knowledge about alternative and supplementary remedies is a main way for enhancing health of patients who suffer from OA disorders. Zingiber zerumbet (Z. zerumbeton) is a kind of herb of the ginger family and is a natural compound with various biomedical characteristics like anti-proliferative, anti-inflammatory, and antioxidant effect. However, Z. zerumbet could be applied for reduction of OA symptoms because of its circulatory stimulant and anti-inflammatory effects. Anyway, up to now there is not any methodical literature review for evaluating the Z. zerumbet clinical effectiveness productiveness in treatment of OA. The main aim of the current study is to review scientific resources around therapeutic effectiveness of Zingiber zerumbet in treatment of adverse symptoms of OA disorder.
Keywords: Anti-inflammatory remedy, ginger, herbal medicine, osteoarthritis (OA), Zingiber zerumbet
|How to cite this article:|
Ahmadabadi HK, Vaez-Mahdavi MR, Kamalinejad M, Shariatpanahi SS, Ghazanfari T, Jafari F. Pharmacological and biochemical properties of Zingiber zerumbet (L.) Roscoe ex Sm. and its therapeutic efficacy on osteoarthritis of knee. J Family Med Prim Care 2019;8:3798-807
|How to cite this URL:|
Ahmadabadi HK, Vaez-Mahdavi MR, Kamalinejad M, Shariatpanahi SS, Ghazanfari T, Jafari F. Pharmacological and biochemical properties of Zingiber zerumbet (L.) Roscoe ex Sm. and its therapeutic efficacy on osteoarthritis of knee. J Family Med Prim Care [serial online] 2019 [cited 2021 Aug 1];8:3798-807. Available from: https://www.jfmpc.com/text.asp?2019/8/12/3798/272468
| Introduction|| |
One of the most frequent forms of arthritis that could affect a lot of people worldwide is osteoarthritis which would be increasing with age and is a kind of chronic disease that would be specified by steady degeneration of the smooth articular cartilage with response of subchondral bone. This disorder could damage health of people worldwide and on the other hand osteoarthritis (OA) would affects human beings with significant disability and morbidity. The novel World Health Organization (WHO) survey uncover that about ten percent of world population with average age of 60 are suffering from OA disorder.
Formerly, it was supposed that OA would be considered as a consequence of both biological and mechanical events which could cause disruption of the normal balance mechanism that could be happen amongst anabolic and catabolic processes within the articular cartilage. Chondrocyte cell within the mature smooth, white tissue of articular cartilage is the unique type of cell which is efficient for maintenance and production of extracellular matrix. Consequently, any decrement in density of chondrocyte cell will cause OA development. Biomechanical estimations specified that the surface zone damage of the smooth, white tissue of articular cartilage could increase the cartilage matrix loading which would be resulting in higher stress on the underlying cartilage tissue and further subchondral reaction (Stoop et al., 2001). On the other hand, various factors like obesity, immobilization of joints and increased age could also cause the development of this disease.
At the present time, there are not any commercially suitable remedies which could be applied for modifying the OA development. However, non-steroidal anti-inflammatory (NSAID) remedies are broadly specified for the OA pain treatment. Anyway, the application of such remedies in long periods of time would cause erosions, platelet aggregation elimination, and ulcers in upper gastrointestinal tract consists of the mouth. As a matter of fact, novel remedies are beneficial for controlling some symptoms like pain. On the other hand, some detrimental side effects would be improved by the application of alternatives of botanical extracts. Plants extracts with pharmaceutical properties have been applied from a long time ago for management of various health disorders. The investigation of various compounds or plant extracts has been popular in several fields of the medicinal and biological sciences.
Various extracts collected from different medicinal plants could have therapeutic effects like anti-cancer, anti-inflammatory, and anti-oxidants which Z. zerumbet is one of this effective plants.,, For instance, zerumbone as a crystalline sesquiterpene which is derived from Z. zerumbet is one of these effective extracts. However, rhizomes of Z. zerumbet have large amount of zerumbone in. Additionally, antioxidant and anticancer actions of zerumbone would be main incentive for investigating if it has chondroprotective properties against OA.
| Materials and Method|| |
A general research of the literature, containing English studies which were published or/and unpublished was administered by application of special study keywords. The liability of publications of foreign languages was included in English language and studies was with adequate details for determining if suitability criteria were met. An extensive research was conducted on some electronic databases including AMED, BioMed central gateway, AARP's AgeLine Database, MEDLINE, DARE, Cochrane library, EMBASE, Dissertations Abstract International, CINAHL Nursing Journal Databases, Cochrane library, Health Source Nursing/Academic edition, International Pharmaceutical Abstract and PubMed. Additionally, some clinical scientific review was investigated for evaluating the productiveness of homeopathic medicinal extracts of ginger amongst patients who suffer from OA disorders. The collected articles were categorized within four main groups including osteoarthritis disorder, Ginger herbalism, Z. zerumbet herbalism and therapeutic effect of Z. zerumbet in treatment of OA symptoms. After elimination of some of unrelated articles, finally 82 related articles were conducted within this comprehensive study. The schematic diagram in which demonstrates various steps of the selection way of this study has shown in [Figure 1] that evidently presents specific domain of the current study.
|Figure 1: The chart of procedure of choosing related articles in current study in accordance with PRISMA method|
Click here to view
The progression of OA is approximately a prolonged procedure and consist of two main stages. The first one is a parser stage where the cartilage erosion would hasten via the creation of matrix digesting enzymes and concurrent reduction in the matrix synthesis. The second one is a multi-step biosynthetic stage which chondrocyte cells attempt for repairing the defective extracellular matrix. In comparison with the ordinary chondrocyte cells, the synthesis-depreciation balance of the matrix is modified in osteoarthritis chondrocyte cells mainly because of:
I: The increment of inflammatory cytokine such as IL-1, TNF-a, IL-6, IL-11 and IL-8.
II: The increment of proteolytic enzymes of metalloproteinases as matrix degrading enzymes (MMPs 1, 2, 3, 7, 8, 13, and 14), cysteine proteinases, serine and extracellular proteolytic enzymes of aggrecanase 1 and 2.
III: free radical's generation such as reactive nitrogen species (RNS) and reactive oxygen species (ROS)
IV: Programmed cell death of apoptosis induction
V: Decrement of synthesis of matrix metalloproteinases (MMP) enzyme inhibitors which known as tissue inhibitor of metalloproteinase (TIMPs)
VI: Decrement of the anabolic factors productions like proteins of bone morphogenetic, naturally growth factors and cytokines.,
Ahmed et al. showed that the inferior inflammatory response discovered within OA is because of the increment of natural dinoprostone which successively cause degradative and inflammatory processes via participating within the collagen synthesis. Therapeutic management using pharmaceutical drugs play a great role in OA and paracetamol, conventional non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors as a NSAI drug and narcotic analgesics remedies are proved to be able in reduction of pain in OA. Anyway, prolonged application of aspirin is proved to raise the risk of Cardiovascular disease (CVD); the usage of cyclooxygenase-2 inhibitors would increase stroke and myocardial infarction risk; using of NSAIDs could cause edema, ulcer disease, nausea, dyspepsia, gastrointestinal bleeding, bloating, hypertension aggravation, renal insufficiency and interstitial nephritis; and additionally narcotic analgesics drugs could cause giddiness, constipation, nausea, mouth dryness, sedation, and so on.,
Overall humankind awareness publicly and within medical community is increasing about the application of alternative or unconventional treatment methods by patients. Patients who suffer from chronic painful disease frequently are searching for alternative remedies and nowadays ginger and its derived extracts are such materials which could be used for treatment of rheumatic disorders. From the ancient time, ginger has been applied for pharmaceutical purposes and particularly it had played an important role in traditional Indian and Chinese medical profession. However, Naheed et al. have shown that ginger could treat rheumatic disorders and also its extracts could be applied for preventing metabolism of arachidonic acid and could affect as antirheumatic or anti-inflammatory agents.
Nowadays such available drugs for treatment of osteoarthritis (OA) are just analgesia agents. The simple analgesics prescription like acetaminophen for reduction of pain commonly, applied before being treated with nonsteroidal anti-inflammatory drugs (NSAIDs). The application of NSAIDs is restricted due to the risk of extra side effects, exclusively renal and gastrointestinal perniciousness.
Ginger clinical advantages
The higher rates of prevalence of chronic OA could have considerable impact on any society economy. On the other hand, the increment of pain frequency could force the patients to use analgesic or anti-inflammatory agents or go under orthopedic surgical procedure. Bookwala et al. reported that patients who suffer from OA disorder will experience depression due to their inappropriate social and physical functioning. However, the depression rate amongst younger people who suffer from arthritis higher than older patients.
In accordance with detrimental psychosocial and physiological consequences of OA disorder and their relative impact on life quality of patients, the proper management of OA could impose a broad range of initiative and healthcare services. Due to the fact that, there is not any universal cure for OA disorder a few number of supplementary, pharmaceutical and surgical remedies are existing which could diminish the OA disorder symptoms. Anyway, the concern about the effectiveness of some of this remedies would increase the mortality and morbidity of patients. Elizabeth et al. reported that non-steroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase-2 inhibitors could enhance the risk of damaging cardiovascular events. It's while, traditional NSAIDs have been shown to enhance the risk of damaging gastrointestinal events.
Furthermore, the most frequent NSAIDs including Ibuprofen, Naproxen and Indomethacin could prevent the release and synthesis of human cartilage matrix proteoglycans in vitro which could speed up the articular cartilage degeneration rate in OA. Anyway, recently there is not any methodical documented review on the efficacy and safety of NSAIDS in OA. However, most of patients have become progressively attentive about the safety of these medical agents and afterwards tried for applying alternative and supplementary treatments for alternative solutions. In accordance with the newest trials, one of the most effective remedies which not proved scientifically but traditionally is prescribed by herb doctors is ginger and its extracts.
One of the most important capabilities of ginger and its extracts is the circulatory stimulant and anti-inflammatory effect which could be effectively used in treatment of OA. Additionally, one of the most important plants in the family of ginger is Zingiber zerumbet that known as bitter ginger which has the same remedial effects on OA disorder like ginger. In accordance with such related experimental studies Z. zerumbet could prevent the intermediary of the pro-inflammatory synthesis including nitric oxide and Prostaglandin-E4 within Leukotriene-B4 and porcine chondrocyte cells in vitro could decrease inflammation and pain level in patients with OA disorder.
The effect of ginger extracts on OA patients
The findings of Al-Saffar et al. study demonstrated that the effectiveness of ibuprofen and ginger extract is higher than placebo in reduction of pain amongst patients who suffer from OA. On the other hand, they reported that the application of NSAIDs in treatment of osteoarthritis would not be without any side effects, but unfortunately the fact is that a lot of patients and medics approve these remedies for various treatment term application. Anyway, the remedial productivity of these remedies would often be restricted due to their side effect development, mainly complications of gastrointestinal ulceration. Complications of peptic ulcer like perforation and bleeding corresponding with NSAID medication mostly happen without any previous warning and could be great threatening for life. The properties of ginger extracts are not known certainly, but investigations around the extracts of lipophilic rhizome have proved that shogaols, gingerols and some possible active components could be achieved.
Inflammation could increase arachidonic acid oxygenation which would be metabolized via 5-lipoxygenase and cyclooxygenase and could be outstanding to leukotriene B4 and prostaglandin E2 which two of them are strong inflammation mediators. However, ginger possess chemical substances with potential of antiinflammatory effect which would be able to have the effects of shogaols, dialdehyd diterpens, diphenylheptanoids and gingerols which could prevent physiologically active lipid compounds inflammation. These agents could prevent of synthesis of signaling molecules which could make the extracted materials more efficient in the rheumatology field. Therefore, the ginger anti-inflammatory efficacy would be because of the decrement of the leukotrienes and prostaglandins formation.,
Alternative and supplementary remedies within the arthritis therapy
OA is a prolonged intense disorder and involves frequent application of therapeutic managements that would have various side effects and invalidate the favorable effects on extended use. Consequently, there is a great demand for effective and safe alternative remedies which would be free of any side effects. On the other hand, Ahmet et al. suggested that the application of alternative and supplementary therapeutic strategies such as traditional medicines (TM), alternative medicine like acupressure and acupuncture, homeopathy, vitamin completion and dietary limitation and also prayer and spiritual healing has been growing between patients who suffer from rheumatic diseases. Additionally, they reported that approximately 48% of adults aged 60 and over who suffer from osteoarthritis use alternative supplementary medicine.
In accordance with reliable sources, the application of herbal remedies like some folk and traditional systems of medication is widely spread. This is due to that plenty of plants have registered details of their application within traditional systems from the ancient past and also are easily obtainable and inexpensive. Z. zerumbet is a kind of plant belonged to the ginger family, has leafy stems and growing to a height of 1.2 m. It arises from Asia originally, but occasionally could be discovered in many tropical countries. Some other ordinary names are including shampoo ginger, bitter ginger, pinecone ginger, and awapuhi. The leaves grow from its branched rhizome and also the flowers that which are similar to orchids, colorless, and would take place within a dense spike-primrose including of multiple overlapping scales upon an extended stalk. Additionally, as reported by Baliga et al. it has been farmed more than thousands of years for pharmaceutical reasons and also as a popular spice.
Ginger phytochemicals properties
Investigation of phytochemical properties of ginger have demonstrated that it's rhizome have a broad range of biologically active compounds. quantitative researches represent that the rhizome has protein, fatty oil, volatile oil, vitamins, ash, water, crude fiber, and various minerals.
Ginger anti-inflammatory effect
Inflammation is a complex procedure which affects both molecular and cellular components and also could actuate extensive variations within the physiological systems. The main characteristics of inflammation are include inactivating mutations, swelling, heat, redness, and pain. Based on the onset and time duration of inflammation, it could be signified as chronic or acute and additionally would be detrimental or beneficial. The time duration of acute inflammation is not long, occur rapidly and is decisive for deflecting infection. On the other hand, chronic inflammation would last longer and frequently is damaging. Inflammation of stratum synoviale would cause multiplication of articular mucosa, cartilage destruction, interpenetrate bone, tendons and ligament tears and could causes in destruction of joints., The ginger anti-inflammatory characteristics have been investigated and evaluated more than hundred years ago. Ojewole et al. have reported that intraperitoneal performance of dried ginger ethanolic extract could interdict the inflammation caused via carrageenans and also induced inflammation of egg albumin. Newly, a specified raw extract of gringer and a small fraction of gingerols in combination with its derivatives have been developed for controlling anti-inflammatory effects upon the genus of gram-positive coccus of rheumatoid arthritis.
Biochemical analytical studies have proved that ginger pacifies synthesis of prostaglandin via prohibition of prostaglandin G/H synthase 1, Prostaglandin-endoperoxide synthase 1, and biosynthesis of leukotriene through preventing arachidonate 5-lipoxygenase. Ginger extract could prevent synthase of prostaglandin-endoperoxide, somehow 8-shogaol and 8-paradol as the main components of ginger could have strong repressive effects on activity of COX-2 enzyme in vitro. The repressive activity of COX-1 enzyme of 8-paradol was shown to be more powerful than within the anti-biofilm agents of gingerol analogs. On the other hand, it has been demonstrated that 8-paradol as the main active flavor element of the seeds of ginger could effectively suppress COX-1, while diphenylheptanoids with groups of 1,2-dihydroxybenzene could be the most active against arachidonate 5-lipoxygenase.
Z. zerumbet various aspects
Ginger family consist of a wide range of species and genres which are distributed mostly in Asia. Various members of this family including ginger, turmeric, Z. zerumbet, and true cardamom are mostly applied in traditional medicine, food flavoring, agriculture, and/or ornamental plants., In accordance with Marlina  reports, plants of the genus zingiber includes nearly 80 species. The major species of genus ginger (Zingiber) is Zingiber officinale Roscoe which biological active compounds include anti-inflammatory properties, pungent constituents of ginger, gingerol, characteristic aroma and flavor. Consequently, this plant mostly would be applied in medical profession and also other purposes related to cooking. Remedial potential of Z. zerumbet maked it possible to investigate its chemical composition. Therefore, Z. zerumbet could produce a combination of large and varied species of organic compounds known as terpenes with a prevalence of sesquiterpenes. Commercially, Z. zerumbet would be used as a pharmaceutical plant with excellent potential of being cultivated without extra prices.
It's extensively proved that a prevalent comprehension about the application of medicinal herbs in medical care of various disease that require to be acknowledged. The traditional application of medicinal herbs would spread the knowledge and could be employed by scientists for investigation around it's pharmacological activities. Norulaini et al. suggested that the rhizome of Z. zerumbet could be used for pharmaceutical purposes. These traditional remedies are commonly produced via fresh rhizome infusion or/and maceration and additionally poultices, tinctures and also various herbals are other remedial applications. On the other hand, Z. zerumbet has a broad range of traditional applications in addition to pharmacological and biological properties.
The rhizome of Z. zerumbet has been broadly applied with significant remedial effects for the remedy of stomach pains, diarrhea, inflammation, flatulence, fever, poisoning, allergies, and bacterial infections. The powder form of rhizome could be applied for treatment of toothache, infections of ear and additionally in form of herbal tea for treating stomach disease. Manpreet et al. have investigated about Z. zerumbet cultivation and reported that it's leaves could be used in treatment of joint inflammation and pain. On the other hand, the cooked rhizome juice is an effective material for preventing worms in children. Additionally, Yu et al. reported that the smooth sticky substance existing within the mature inflorescence, is full of surfactants and could be used as a natural shampoo.
Herbal biology description
Z. zerumbet is a perennial of the nature of a tuber herb which could be discovered naturally like spread plants within shady and damp parts of mountain slopes or lowlands. This plant could be discovered near water sources, rivers, and waterfalls. However, it could be characterized via it's stems which are nearly 1.5 m high that are round, straight, and are coated with flat leaves sheaths. The cluster and leaves grow up from an underground stem or a thick rhizome. The clusters of flowers are green when they are young would become red when grew up and became old and their height will reach about 10 cm. As one of the main botanical characteristics of Z. zerumbet it could be noted that it's yarn is linked with a long beak which is curved. Additionally, as Yob et al. mentioned the seeds of this herb are black and ellipsoids, it's rhizome is thick, yellow, aromatic, and perennial.
Z. zerumbet chemical mixture
Z. zerumbet is combined from various compounds which belong to a broad range of chemical metabolites like terpenes, polyphenols and alkaloids. Terpenes are a broad and various category of organic compounds which could be produced via plenty of plants particularly coniferophyta. One of the main compounds of Z. zerumbet is zerumbone which could be derived from urgent Z. zerumbet oil and also certify its structure. Zerumbone is a sesquiterpene with one ring of atoms in its molecule which has three double bonds  [Figure 2].
|Figure 2: Chemical composition of zerumbone. Derived in accordance with Adriana et al.|
Click here to view
The remedial characteristics of the active compositions derived from the rhizome have been applied for treatment of such major disorders like stomach disease. On the other hand, it has been proved that they would have antiinflammatory, antibacterial, antitumoral, antiviral, painkiller, and antioxidant properties.,, Specific biochemical interactions which could point out the characteristics of genuine zerumbone and rhizome derived juice with various dissolvent are mentioned in [Table 1].
|Table 1: Several pharmacological activities of Z. zerumbet. Derived in accordance with Adriana et al.|
Click here to view
In accordance with Zakaria et al. Z. zerumbet could prevent the prostaglandin-endoperoxide synthase (PTGS) activity within both central nervous and peripheral system and also the inflammatory mediator's synthesis. On the other hand, Somchit et al. during their study have worked around two different models of anti-inflammatory constituents of Z. zerumbet consist of macrophage cell culture and paw edema. The remedial management of RAW 264.7 macrophages cells with zerumbone combinations and isolated 3-O-methyl quercetin and kaempfero would offer the most effective prevention of the inflammatory mediator's production. Additionally, Adriana et al. have investigated anti-inflammatory and anti-hypersensitive activities of water extract of Z. zerumbet for recognizing its anti-inflammatory effect within vivo and vitro. Peritoneal cells of macrophages picked up from albino BALB/c mice and applied for evaluating the cytokines of IL-4 and tumor necrosis factor of TNFα.
Z. zerumbet biomedical applications
Various parts of plants have been applied within human diet from thousands of years ago. Different parts of plant including flowers, stems and leaves are applied for improving the odor, taste, color, and also the food quality. Additionally, recent methodical experiments and researches have demonstrated the supernatural characteristics of herb extracts and also their derived spices and seasoning as antimicrobial, anti-oxidative, and/or preservative agents. Due to the increment of such disorders like cancer, patients, and specialists would try for finding alternative and supplementary remedies for treating the disorder. Pharmaceutic plants that are contained within group of alternative and complementary medicine because of their content of active different biologically active compounds have the potential of curing some special disorders. In accordance with Shanmugam et al. research, a diet which is full of fruits, herbs and seeds which contain essential pharmaceutical compounds would not have any damaging side effects and optimistically could help in prevention and also treatment of cancer. One of these rich plant which has a lot of pharmaceutical effects is Z. zerumbet and its extracts that could be achieved from its rhizome. Sosmitha et al. within their study around biomedical characteristics of Z. zerumbet treatment of cancer reported that this plant has been applied for treatment of arthritis and muscular pain due to the fact that it has anti-inflammatory compounds. On the other hand, it would be beneficial for treating severe headaches, ulcers, and high cholesterol.
Anti-inflammatory effects of Z. zerumbet
Somchit et al. during their study by studing around the effects of Z. Zerumbone derived from Zingiber zerumbet on reduction of pain and inflammation reported that Z. Zerumbone have great anti-inflammatory capabilities. Akkaya et al. have worked on the effect of Z. zerumbet on tissue compatibility type II cells in osteoarthritic joint synovial stratum and reported that Z. zerumbet could prevent antigen-presenting cells (APCs) of immune and also decrease the osteoarthritis inflammatory process. Somchit et al. and Hosseinpour et al. have worked on the application of Z. zerumbet due to its anti-inflammatory and analgesic characteristics and reported that, Z. zerumbet powerfully could prevent inflammation via lambda carrageenan and dinoprostone which was comparable to the nonsteroidal anti-inflammatory drug of the oxicam class. Additionally, they demonstrated that Z. zerumbet could prevent pain just alike to the NSAIDs. Zakaria et al. have investigated anti-inflammatory and antinociceptive of Z. zerumbet on arthritis. The reported that Z. zerumbet has the capability of prevention of prostaglandin-endoperoxide synthase (PTGS) and nitric oxide synthase (iNOS) in addition with dinoprostone.
The application of Z. zerumbet could increase the proliferation and polarization of T cell via endotoxin motivated the soft gelatinous tissue inside some bones derived dendritic cells within an allogeneic test of mixed lymphocyte reaction. Additionally, Shieh et al. reported that Z. zerumbet could acts as anti-allergic agents upon viamodulation of cytokines of T-cell subsets. Al-saffar et al. have worked around the productiveness of Z. zerumbet on increment of the immune reaction caused by an antigen within the synovial membrane in the monosodium iodoacetate model of osteoarthritis pain. Their outcomes proved that the application of Z. zerumbet could decrease the OA symptoms and improve the reaction of immune.
Z. zerumbet clinical applications for treatment of OA
Al-Saffar et al. have worked around the remedial effects of Z. zerumbet on patients who suffer from osteoarthritis. They reported that, Z. zerumbet could be applied for reduction of rheumatological pain and also attempted to confirm the Z. zerumbet role in reduction of joint pain such as OA. Additionally, at their study Al-Saffar et al. demonstrated that the application of Z. zerumbet was obviously more advantageous than response of placebo in treatment of such disorder. Ganabadi et al. have investigated around the effects of zerumbones as the main extract of Z. zerumbet on the treatment of osteoarthritis and reported that, the application of this remedy does not have any serious side effects. Additionally, they noted that this plant could easily mitigate edema and pain in patients who suffer from rheumatoid arthritis (RA) and OA disorder without having any adverse side effects during the period on application.
| Conclusion|| |
Osteoarthritis (OA) is a degenerative joint disease, which is associated with increased pain and disability, and a simultaneous decline in the quality of life of sufferers. Various number of scientific experiments have investigated the application of the best knowledge of productiveness of Z. zerumbet in OA disorder, although the findings of these studies are not compatible. In accordance with the last researches, not any special cure is existing for OA. It's while there are multiple remedies for reduction symptoms of patients who suffer from disorders and related inabilities which could enhance their life quality. Remedies which have been applied for a long time for treatment of OA have newly discovered to induce injury to some patients. On the other side, additional knowledge about alternative and supplementary remedies is a main way for enhancing health of patients who suffer from OA disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently are applied for symptomatic treatment of the disease and are linked with various side effects which would increase the attention to alternative remedy options. Z. zerumbet is a plant which could be frequently applied for reduction of OA symptoms because of its circulatory stimulant and anti-inflammatory effects.
Zingiber zerumb et al.so known as bitter ginger is an aromatic, tuberose plant which is perennial and grows within humid climates. Z. zerumbet traditionally could be discovered all over Asia where it is broadly applied within drink, foods and also as ornamental plants. The sticky liquid existing in the clusters of this plant is containing surfactants which could be applied as a hair shampoo.
The chemical composition of Z. zerumbet is mainly composed of polyphenols and terpenes. Zerumbone is a sesquiterpenoid with biological effects and broadly being investigated for its pharmaceutical properties. The substances and liquids extracted from Z. zerumbet are having such properties including antiviral, antimicrobial, anti-inflammatory, antidiabetic, analgesic, anticancer, and antioxidant. Additionally, Z. zerumbet could be applied as advantageous and safe remedies for decreasing the pain intensity and consequently could improve functional capacity of patients who suffer from OA disorder. Due to the fact that the prevalent documents around the effectiveness of this herbal remedies is not convincing enough, additional researches are required for determining if Z. zerumbet is more impressive than any other remedies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: Mechanisms of action. Arthritis Res Ther 2003;5:54-67.
Dumond, H, Presle, P, Pottie, S, Pacquelet S, Terlain B, Netter P, et al
. Site specific changes in gene expression and cartilage metabolism during early experimental osteoarthritis. Osteoarthritis Cartilage 2004;12:284-95.
McDougall JJ. Arthritis and pain. Neurogenic origin of joint pain. Arthritis Res Ther 2006;8:220.
Charlesworth J, Fitzpatrick J, Perera NKP, OrchardJ. Osteoarthritis- a systematic review of long-term safety implications for osteoarthritis of the knee. BMC Musculoskelet Disord 2019;20:151.
Australian Institute of Health and Welfare (AUS) Osteoarthritis. Canberra: Australian Institute of Health and Welfare; 2016.
Bove SE, Calcaterra RM, Brooker CM, Huber CM, Guzman RE, Juneau PL, et al
. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthritis Cartilage 2003;11:821-30.
Tesfahuneygn G, Gebreegziabher G. Medicinal plants used in traditional medicine by ethiopians: A review article. J Respir Med Lung Dis 2019;4:1040.
Sakinah SA, Handayani ST, Hawariah LP. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio. Cancer Cell Int 2007;7:4-4.
Ruslay S, Abas F, Shaari K, Zainal Z, Maulidiani, Sirat H, et al
. Characterization of the components present in the active fractions of health gingers (Curcuma Xanthorrhiza and Zingiber zerumbet by HPLC-DAD ESIMS. Food Chem 2007;104:1183-91.
Abdul AB, Abdelwahab SI, Bin Jalinas J, Al-Zubairi AS, Taha MM Combination of zerumbone and cisplatin to treat cervical intraepithelial neoplasia in female BALB/c mice. Int J Gynecol Cancer 2009;19:1004-10.
Kalantari K, Moniri M, Boroumand Moghaddam A, Abdul Rahim R, Bin Ariff A, Izadiyan Z, et al
. A review of the biomedical applications of zerumbone and the techniques for its extraction from ginger rhizomes. Molecules 2017;22:E1645.
Losina E, Weinstein AM, Reichmann WM, Burbine SA, Solomon DH, Daigle ME, et al
. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res (Hoboken) 2013;65:703-11.
Australian Commission on Safety and Quality in Health Care (AUS) Osteoarthritis of the knee clinical care standard. Sydney: Australian Commission on Safety and Quality in Health Care; 2017.
Ahmed S, Anuntiyo J, Malemud CJ, Haqqi TM. Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: A review. Evid Based Complement Alternat Med 2005;2:301-8.
Ragle RL, Sawitzke AD. Nutraceuticals in the management of osteoarthritis: A critical review. Drugs Aging 2009;29:717-31.
Kotlarz H, Gunnarsson CL, Fang H, Rizzo JA. Insurer and outof-pocket costs of osteoarthritis in the US: Evidence from national survey data. Arthritis Rheum 2009;60:3546-53.
Alrowais NA, Alyousefi NA. The prevalence extent of complementary and alternative medicine (CAM) use among Saudis. Saudi Pharm J 2017;25:306-18.
Rheumatology Expert Group (AUS) Therapeutic guidelines. Rheumatology-version 3. Melbourne: Therapeutic Guidelines Limited; 2017.
Aryaeian N, Shahram F, Mahmoudi M, Tavakoli H, Yousefi B, Arablou T, et al
. The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis. Gene 2019;698:179-85.
Bartels EM, Folmer VN, Bliddal H, Altman RD, Juhl C, Tarp S, et al
. Efficacy and safety of ginger in osteoarthritis patients: A meta-analysis of randomized placebo-controlled trials. Osteoarthritis Cartilage 2015;23:13-21.
Bookwala J, Harralson TL, Parmelee PA. Effects of pain on functioning and well-being in older adults with osteoarthritis of the knee. Psychol Aging 2003;18:844-50.
Dominick K, Ahern FM, Gold CH, Heller DA. Health-related quality of life and health service use among older adults with osteoarthritis. Arthritis Rheum 2004;51:326-31.
Elizabeth C, Nicholas F, Sarah S. Safety of cyclooxygenase-2 inhibitors in osteoarthritis: Outcomes of a systematic review and meta-analysis. Drugs Aging 2019;36(Suppl 1):25-44.
Ross AH. The acceleration of articular cartilage degeneration in osteoarthritis by nonsteroidal anti-inflammatory drugs. J Prolotherapy 2010;1:305-22.
Bally M, Dendukuri N, Rich B, Nadeau L, Helin-Salmivaara A, Garbe E, et al
. Risk of acute myocardial infarction with NSAIDs in real world use: Bayesian meta-analysis of individual patient data. BMJ 2017;357:j1909.
Shen CL, Hong KJ, Kim SW. Comparative effects of ginger root (Zingiber officinale Rosc.) on the production of inflammatory mediators in normal and osteoarthrotic sow chondrocytes. J Med Food 2005;8:149-53.
Al-Saffar FJ, Ganabadi S, Fakurazi S, Yaakub H, Lip M. Chondroprotective effect of zerumbone on monosodium iodoacetate induced osteoarthritis in rats. J Appl Sci 2010;10:248-60.
Baliga MS, Haniadka R, Pereira MM, D'Souza JJ, Pallaty PL, Bhat HP, et al
. Update on the chemopreventive effects of ginger and its phytochemicals. Crit Rev Food Sci Nutr 2011;51:499-523.
Ganabadi S, Fakurazi S, Kadir AA. Zerumbones effect on major histocompatibility complex type II cells in synovial membrane of osteo arthritic joint. Res J Vet Sci 2009;2:14-20.
Karadağ A, Hayta E, Kaptanoğlu E, Konak A. Complementary and alternative treatment methods in chronic rheumatic diseases in the Central Anatolia. Electron J Gen Med 2018;15:em60.
Baliga MS, Haniadka R, Pereira MM, D'Souza JJ, Pallaty PL, Bhat HP, et al
. Update on the chemopreventive effects of ginger and its phytochemicals. Crit Rev Food Sci Nutr 2011;51:499-523.
Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber offcinale Roscoe): A review of recent research. Food Chem Toxicol 2008;46:409-20.
Rahmani AH, Shabrmi FM, AlySM. Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities. Int J Physiol Pathophysiol Pharmacol 2014;6:125-36.
Arulkumar R, Bang EJ, Noh S-G, Yokozawa T, Chung HY. Role of garlic and ginger in anti-oxidative and anti-inflammatory effects in aging. SDRP J Food Sci Technol 2019;4. doi: 10.25177/jfst.4.5.mr.533
Ojewole JA. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber offcinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. Phytother Res 2006;20:764-72.
Herve T, Raphaël KJ, Ferdinand N, Victor Herman N, Willy Marvel NM, Cyril D'Alex T, et al
. Effects of ginger (Zingiber officinale, Roscoe) essential oil on growth and laying performances, serum metabolites, and egg yolk antioxidant and cholesterol status in laying Japanese quail. J Vet Med 2019;2019:7857504.
Ouboussad L, Burska AN, Melville A, Buch MH. Synovial tissue heterogeneity in rheumatoid arthritis and changes with biologic and targeted synthetic therapies to inform stratified therapy. Front Med (Lausanne) 2019;6:45.
Irfan S, Nawaz Ranjha MMA, Mahmood S, Mueen-ud-Din G, Rehman S, Saeed W, et al
. A critical review on pharmaceutical and medicinal importance of ginger. Acta Sci Nutr Health 2018;3.
Solanky RU, Patel SR, Patel JR. In vitro
regeneration of ginger (Zingiber officinale Rosc.) through callus culture. AGRES – An Int e-Journal 2:196-202.
Jamal A, Javed K, Aslam M, Jafri MA, Gastroprotective effect of cardamom, Elettaria cardamomum Maton. fruits in rats. J Ethnopharmacol 2006;103:149-53.
Andreo D, Jorge N. Capacidade antioxidante e estabilidade oxidativa de Zingiber officinale. Cient Ciênc Biol Saúde 2011;13:33-7.
M Ardiyani. New species of zingiber (Zingiberaceae) from Enggano Island, Indonesia. REINWARDTIA 2016;14:307-10.
Yu F, Harada H, Yamasaki K, Okamoto S, Hirase S, Tanaka Y, et al
. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett 2008;582:565-72.
Deb L, Singh KR, Singh KB, Thongam B. Some ethno-medicinal plants used by the native practitioners of chandel district, Manipur, India. Int Res J Pharm 2011;2:199-200.
Norulaini NAN, Anuar O, Omar AKM, Alkarkhi AFM, Setianto WB, Fatehah MO, et al
. Optimization of SC–CO2 extraction of zerumbone from Zingiber zerumbet (L.) Smith. Food Chem 2009;114:702-5.
Kigen G, Kamuren Z, Njiru E, Wanjohi B, Kipkore W. Ethnomedical survey of the plants used by traditional healers in Narok County, Kenya. Evid Based Complement Alternat Med 2016:8976937. doi: 10.1155/2019/8976937.
Sidahmed HM, Hashim NM, Abdulla MA, Ali HM, Mohan S, Abdelwahab SI, et al
. Antisecretory, gastroprotective, antioxidant and anti-helicobcter pylori activity of zerumbone from Zingiber zerumbet (L.) Smith. PLoS One 2015;10:e0121060.
Ghosh S, Majumder PB, Mandi SS. Species-specific aflp markers for identification of Z. officinale, Z. montanum and Z. zerumbet (Zingiberaceae). Genet Mol Res 2011;10:218-29.
Jaidka M, Kaur R, Sepat S. Scientific cultivation of ginger (Zingiber officinalis). Indian Agricultural Research Institute New Delhi–110 012. Advances in Vegetable Agronomy. 2018. Chapter32.
Tzeng TF, Liou SS, Chang CJ, Liu IM. The ethanol extract of Zingiber zerumbet attenuates streptozotocin-induced diabetic nephropathy in rats. Evid Based Complement Alternat Med 2013;2013:340645. doi: 10.1155/2013/340645.
Yob NJ, Jofrry SM, Affandi MM, Teh LK, Salleh MZ, Zakaria ZA. Zingiber zerumbet (L.) Smith: A review of its ethnomedicinal, chemical, and pharmacological uses. Evid Based Complement Alternat Med 2011;2011:543216. doi: 10.1155/2011/543216.
Chang CJ, Tzeng T, Chang Y, Liu I. Beneficial impact of Zingiber zerumbet on insulin sensitivity in fructose-fed rats. Planta Med 2012;78:317-25.
Santosh Kumar SC, Srinivas P, Negi PS, Bettadaiah BK. Antibacterial and antimutagenic activities of novel zerumbone analogues. Food Chem 2013;141:1097-103.
Sahu AK, Panda C, Nayak BS. Determination of phytochemical and anthelmintic activity of rhizome of Zingiber zerumbet. J Pharm Adv Res 2018;1:399-402.
Jalil M, Mohamad Annuar MS, Tan BC, Khalid N. Effects of selected physicochemical parameters on zerumbone production of Zingiber zerumbet Smith cell suspension culture. Evid Based Complement Alternat Med 2014:757514. doi: 10.1155/2015/757514.
Santosh Kumar SC, Srinivas P, Negi PS, Bettadaiah BK. Antibacterial and antimutagenic activities of novel zerumbone analogues. Food Chem 2013;141:1097-103.
Rout OP, Acharya R, Mishra SK.In vitro
antioxidant potentials in leaves of coleus aromaticus benth and rhizomes of Zingiber zerumbet (L.) Sm. J Appl Pharm Sci 2011;1:194-8.
Takada Y, Murakami A, Aggarwal BB. Zerumbone abolishes NF-κB and IκBα kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion. Oncogene 2005;24:6957-69.
Sung B, Jhurani S, Ahn KS, Mastuo Y, Yi T, Guha S, et al
. Zerumbone down-regulates chemokine receptor CXCR4 expression leading to inhibition of CXCL12-induced invasion of breast and pancreatic tumor cells. Cancer Res 2008;68:8938-44.
Park JH, Park GM, Kim JK. Zerumbone, sesquiterpene photochemical from ginger, inhibits angiogenesis. Korean J Physiol Pharmacol 2015;19:335-40.
Phongpaichit S, Vuddhakul V, Subhadhirasakul S, Wattanapiromsakul C. Evaluation of the antimycobacterial activity of extracts from plants used as self-medication by AIDS patients in Thailand. Pharm Biol 2006;44:71-5.
Voravuthikunchai SP, Limsuwan S, Supapol O, Subhadhirasakul S. Antibacterial activity of extracts from family Zingiberaceae against foodborne pathogens. J Food Safety 2006;26:325-34.
Somchit MN, Shukriyah MHN, Bustamam AA, Zuraini A. Anti-pyretic and analgesic activity of Zingiber zerumbet. Int J Pharm 2005;1:277-80.
Sriphana U, Pitchuanchom S, Kongsaeree P, Yenjai C. Antimalarial activity and cytotoxicity of zerumbone derivatives. Sci Asia 2013;39:95-9.
Zakaria ZA, Mohamad AS, Chear CT, Wong YY, Israf DA, Sulaiman MR. Antiinflammatory and antinociceptive activities of Zingiber zerumbet methanol extract in experimental model systems. Med Princ Pract 2010;19:287-94.
Hashemi SR, Zulkifli I, Hair Bejo M, Farida A, Somchit MN. Acute toxicity study and phytochemical screening of selected herbal aqueous extract in broiler chickens. Int J Pharmacol 2008;4:352-60.
Bustamam A, Ibrahim S, Al-zubairi AS, METM, Mohan S. Zerumbone: A natural compound with anti-cholinesterase activity. Am J Pharm Toxicol 2008;3:209-11.
Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Ming OH, Khalid S, et al
. Zerumbone-induced antinociception: Involvement of the L-argininenitric oxide-cGMP-PKC-K+ATP channel pathways. Basic Clin Pharmacol 2010;108:155-62.
Abdelwahab SI, Abdul AB, Zain ZNM, Hadi AHA. Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells. Int Immunopharmacol 2012;12:594-602.
Taha MME, Abdul AB, Abdullah R, Ibrahim TA, Abdelwahab SI, Mohan S. Potential chemoprevention of diethylnitrosamine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger (Zingiber zerumbet). Chem Biol Interact 2010;186:295-305.
Somchit MN, Mak JH, Ahmad Bustamam A, Zuraini A, Arifah AK, Adam Y, et al
. Zerumbone isolated from Zingiber zerumbet inhibits inflammation and pain in rats. J Med Plants Res 2012;6:177-80.
Koga AY, Beltrame FL, Pereira AV. Several aspects of Zingiber zerumbet: A review. Rev Bras Farmacogn 2016;26:385-91.
Singh G, Kapoor I, Singh P, de Heluani CS, de Lampasona MP, Catalan CA. Chemistry, antioxidant and antimicrobial investigations on essential oil and oleoresins of Zingiber officinale. Food Chem Toxicol 2008;46:3295-302.
González-Lamothe R, Mitchell G, Gattuso M, Diarra MS, Malouin F, Bouarab K. Plant antimicrobial agents and their effects on plant and human pathogens. Int J Mol Sci 2009;10:3400-19.
Jones E, Nissen L, McCarthy A, Steadman K, Windsor C. Exploring the use of complementary and alternative medicine in cancer patients. Integr Cancer Ther 2019;18:1534735419854134.
Kubatka P, Kello M, Kajo K, Kruzliak P, Výbohová D, Mojžiš J, et al
. Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model. Eur J Nutr 2017;56:1303-16.
Shanmugam MK, Lee JH, Chai EZ, Kanchi MM, Kar S, Arfuso F, et al
. Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds. Semin Cancer Biol 2016;40-41:35-47.
Girisa S, Shabnam B, Monisha J, Fan L, Halim CE, Arfuso F, et al
. Potential of Zerumbone as an anti-cancer agent. Molecules 2019;24:E734. doi: 10.3390/molecules24040734.
Akkaya B, Oya Y, Akkaya M, Al Souz J, Holstein AH, Kamenyeva O, et al
. Regulatory T cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells. Nat Immunol 2019;20:218-31.
Hosseinpour M, Ahmad Bustamam A, Rahman HS, Rasedee A, Yeap SK, Ahmadi N, et al
. Comparison of apoptotic inducing effect of zerumbone and zerumbone-loaded nanostructured lipid carrier on human mammary adenocarcinoma Mda-mb-231 cell line. J Nanomater 2014:182. doi: 10.1155/2014/742738.
Shieh YH, Huang HM, Wang CC, Lee CC, Fan CK, Lee YL. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced th2 responses and airway inflammation in mice. Int Immunopharmacol 2015;24:383-91.
Al-Saffar F, Ganabadi S, Fakurazi S, Yaakub H. Zerumbone significantly improved immunoreactivity in the synovium compared to Channa striatus extract in monosodium iodoacetate (MIA)-induced knee osteoarthritis in rat. J Med Plants Res 2011;5:1701-10.
[Figure 1], [Figure 2]