Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

Книга_5327_Библиотеки_им_академика_М_И_Перельмана

.pdf

Скачиваний:

Добавлен:

30.08.2026

Размер:

52 Мб

Скачать

☆

<<< < Предыдущая 12 13 14 15 16 17 18 19 20 21 22 2324 / 5024 25 26 27 28 29 30 31 32 33 34 35 36 > Следующая >>>

224

https://t.me/medicina_free

In Java, the procedure is to plant Cinchona on terrace in which a sump hole was dug on the rear end of the terrace every metre or two for aeration and to gather eroded soil and water, then dig these holes out when lled and pile the dirt on the terrace behind. In this procedure of planting, labour is numerous and inexpensive, so it is proved to be an excellent strategy [9].

S. Aslam etal.

10.6 Planting

The planting area should be cleaned a year ahead of time and shade trees such as Silver oak and or dedabs should be planted. Pits of 30 x 30 x 45cm are excavated and lled with topsoil and other organic waste that has decomposed properly. When seedlings are around a year old, they are transplanted onto the main eld at a spacing of 1.251.25m. When there is enough moisture in the eld, transplanting can be done at any time. The third option is to use high density planting, which involves spacing trees at 1.01.25m or 8000 plants per hectare and gradually harvesting until only 800 plants/ha remain after 25years.

In Darjeeling, seedlings are planted early in the monsoon season (June), with 4–6 pairs of leaves along with them. This increases the chance of their survival. On the bases of slope, pits with dimensions of 1.2m×1.2m×2.0m×2.0m were dug. To achieve clean erect boles, seedlings with dirt stuck to the roots are planted and anchored. In general, 3000 plants per hectare are planted, freeing up space for shade trees. After the fourth year, trees begin to blossom. Trees that have been debudded have more laminar growth and alkaloid content [10].

10.7 Manuring

115kg of nitrogen and potassium, as well as 15kg of phosphorus per hectare are required each year to fertilize the plants of cinchona. Liming at 1.0–1.5 t/ha is advised every 3–4years when the soil pH falls below 4.5.

10.8 Ecology

Some Lepidoptera species, such as the engrailed, the commander, as well as species of the genus Endoclita, including as E. purpurescens, E. sericeus, and E. damor, utilise Cinchona species as food plants. Cinchona pubescens has spread uncontrollably on certain islands, together with the Galapagos, posing a threat to native plant species [11]. It thrives in Ecuador’s native range in volcanic soil rich in organic matter, as well as in highly rocky locations where the roots are open to the air. It thrives in disturbed environments, particularly regions where vegetation has been burned.

10 Cinchona

https://t.me/medicina_free

225

10.9 Pest andDiseases

Any fungal impurity that can be the reason of fast deterioration or loss of immature juicy seedlings is referred to as damping off. The illness has a global distribution and affects many people working in nurseries and greenhouses. Fungi that cause damage are ubiquitous in the soil, and when moisture and temperature circumstances are appropriate, fungal hyphae attack host plants by directly invading the host tissues. Certain damping off species target a wide range of hosts, whilst some have more restricted host range [12, 13]. Various diseases found on this plant species can be classied as the diseases caused by damping off. Fungus infection is more likely to develop in cinchona seedbeds immediately after the seeds have begun to germinate.

In French Guinea, it was observed that a severe seedling wilt of Cinchona ledge- riana and Cinchona succirubra. When the cotyledons were about 4–5mm long, seeds in the seedbeds withered and perished in clumps. In the soil of the damaged patches, many white rhizomorphs of a tropical Clitocybe species were discovered, and when they came into contact with the cinchona rootlets, the rhizomorphs generated mycelial threads that pierced the host tissues [14].

Pestalozzia is a disease that affects cinchona plants in Pala Sumatra and is caused by Pestalozzia myristicae [15]. Infected plants should be removed and burned as soon as possible.

Copper-based fungicides are effective when applied to the soil and help in the removing and burning of the infected plants. Because cinhophyllene-type indole alkaloids along with tiny levels of 5-methoxy-tryptamine present in juvenile Cinchona ledgeriana plants that cause the reduction in insect damage. These chemicals give developing plants a chemical defense against herbivorous insects [16]. Caterpillars of Catalpa sphinx as well as Helopeltis spp., on the other hand, inict harm to nursery plants. The infestation is controlled by spraying dimethyl phosphoric ester. Disphinctus humeralis, a leaf beetle that attacks fragile foliage on occasion, may be controlled using a 0.2% malathion spray.

10.10 Important Chemical Constituents ofCinchona

The genus Cinchona, comprising about 40 species [23], the widely known species include C. calisaya, C. ledgeriana, C. ofcinalis, and C. pubescens (C. succirubra) [24], which contain many biologically active substances. The bark is the primary component that is utilized for various therapeutic and other applications [3]. Previous phytochemical studies revealed a variety of secondary metabolites, including polyphenols(henolic acids, anthocyanins, and avonoids), quinoline alkaloids, and indole alkaloids [23]. In addition, various essential oils and minerals, such as triterpene, organic and phenolic acids (quinic acid, caffeic acid), aveniods and phytosterols are present in the bark [3]. Cinchona alkaloids are among the most

226

https://t.me/medicina_free

S. Aslam etal.

familiar natural products isolated so far. They are separated from numerous species of genus cinchona such as Cinchona succirubra, Cinchona ledgeriana, and Cinchona calisaya, all of which are members of Rubiaceae family [4].

10.11 Cinchona Alkaloids

Alkaloids are secondary metabolites that have the ability to create a variety of medications with signicant pharmacological effects. They are also utilized to investigate physiological responses and biochemical processes of action [25]. Cinchona bark of different species contains more than 36 distinct alkaloids, with quinine (1), quinidine (2), cinchonidine (3), and cinchonine (4) being the most signicant. These four phytochemical components of bark are stereoisomers of one another. The quantity of alkaloids in the bark varies from 7% to 12%, with quinine being the most abundant and making up as much as 90% of it. Moreover, there is signicant variety in alkaloid content and composition both within and between species. Quinine, cinchonidine, and the total amounts of the four main alkaloids, appear to be related to chronology [27]. Cinchona bark is high in quinoline alkaloids, accounting for 6–10% of total quinoline alkaloids. The species with the highest quinine contents are Cinchona ofcinalis, Cinchona ledgeriana, and Cinchona calisaya. Cinchona pubescens possesses a greater percentage of cinchonine (3.3–3.4%) among its higher total alkaloids (6.0–8.2%). Maximum amount of Cinchonidine (3.7–4.9%) is present in the bark of Cinchona kartamanahs when they are over 12years old, and it is similarly high (2.1–2.2%) in the bark of “Hybrida” when it is approximately 6–8years old [17] (Fig.10.1).

In the bark of cinchona, the most essential and distinctive alkaloids comprise 16% quinine (C20H24N2O2), although the amount uctuates (6–10%) depending on the species variation. A typical sample of dried cinchona or the bark of this plant was reported to have 0.4–4% of cinchona. It is often employed as an anti-malarial agent, as well as a avouring component in carbonated beverages, a skeletal muscle relaxant, a treatment for haemorrhoids and varicose veins, and as an oxytoxic agent [3]. Quinine is separated as quinine sulphate from the total alkaloids. It’s a white, sparkling, odourless substance with a strong bitter avour. In water, it is just slightly soluble, but it shows extreme solubility towards organic solvents. In addition to quinine salts, cinchona febrifuge (powder), which is made up of residual alkaloids after quinine removal, is sold [18]. After quinine, the second most prominent alkaloid found in cinchona is cinchonine (C anti-malarial medication [19] with lesser toxic effect and stronger activity than other quinine-related compounds [20]. Another major alkaloid is quinidine, a diastereoisomer of quinine, which is found in cinchona bark in concentrations ranging from 0.25% to 3.0%. It’s a dextrorotatory quinine stereoisomer. Its primary role is to operate as an anti-malarial drug, but it is also effective as an anti-arrhythmic agent [21] when antiarrhythmic metabolism is achieved by membrane stability. Cinchonidine (C

O) is found in most cinchona bark types, particularly in the

19H22N2

O), which is also employed as an

19H22N2

10 Cinchona

https://t.me/medicina_free

227

Powdered crudedrug+ NaOH+CaO +H2O

AqueousLayer

(Cinchonine)

Evaporatetodryness, extract with ethanoland

thedecolorizeand allow it to crystallizeslowly

Cinchonidine

Filter whilehot

Filterate

Precipitateof Cinchonidine Tartrate

AddHCl and then addNH

Cinchonidine

HotFilterate

Ethereal layer (Quinidine + Cinchonidine)

Chillthe Clear Filterate

Extractwithdil.HCl

Then neutralize the acid solution

Alkaloids Bisulphate

Alkaloidssulphate,

Filter

Boil with Actirated ChareoallPowder

Ppts of QuinineSulphate

Addboiling H andNa

Quinine

Filterateof QuinidineTartrate

AddKIand then addNH

Quinidine

90°C



Alkalify pH 6.5

Fig. 10.1 Diagrammatic illustration of Isolation of cinchona alkaloids

bark of C. pusescensval and C. pitayensis, and is primarily utilised as an antimalarial drug. It is a stereoisomer and pseudo-enantiomer of cinchonine that is mostly utilized as an alternative of quinine. Epicinchonidine is frequently used to treat malaria [4]. In the lack of an economically feasible synthetic technique for their synthesis, cinchona bark remains the source of these phytochemicals [22].

Quinolone and quinuclidine rings with a vinyl group are also found. In addition to alkaloids, the bark also includes a colouring substance (up to 10%), polyphenols, avonoids, and an essential oil. [18]. Quiniarnine, cinchotine, hydroquinine, hydrocinchonidine, and cinchotannic acid are some of the other phytochemical constituents found in cinchona (Fig.10.2). The methoxy group is present in quinine and quinidine, but it is absent in chichonine and cinchonidine. Cinchona also contains bitter glycosides and starch granules. Calcium oxalate and crystalline acids like quinic acid are also present. They have a total alkaloids content of at least 6.5%. Quinine accounts for 30–60% of total alkaloids.

In addition to them, a variety of other alkaloids with similar structural relationships have also been discovered such as, cinchotoxine (5), remijinine (6),

228

apo-quinine

Beta-Isoquinidin

https://t.me/medicina_free

N N

OOHO

S. Aslam etal.

H3C

H3CO

Quinolone

Cinchotine

H2C

HO OH

Cupreine

OCH

Quiniarnine

H3C

H3CO

Hydrocinchonidine

Cupreidine

H2C

H3CO OH

epi-quinine

Hydroquinine

OHHO

Cinchotannic acid

Beta-Isocupreidine

H3CO

Fig. 10.2 Structures of potent phytochemicals in Cinchona Plant

cinchonamine (7),quinamine (8), liriodenine (9), lyscamine (10), cinchophylline (11), 9-epiquinine (12),9-epiquinidine (13),dihydroquinine (14),dihydroquinidine (15), quinidineN(4)oxide (16), cinchonicinol (17), Epidihydrocinchonidine (18),Epivinylquinidine (19),Chloroquine (20),Quinotoxin (21) [4, 23] (Fig.10.3).

10 Cinchona

https://t.me/medicina_free

229

H N

NH H N

OMe

Fig. 10.3 Structures of Cinchona Alkaloids and derivatives

230

https://t.me/medicina_free

The bark and roots of the plant contain the majority of the cinchona alkaloids, while cinchophyllines have been found in the leaves [28]. In the bark, a portion of Cinchona alkaloids exist as the salts of acids (quinic acid, cinchotannic acid, etc.). Examination of the leaves of distinct Cinchona tree species revealed that they differ noticeably in the content of alkaloids. For instance, C. “ledgeriana” includes mostly indole type alkaloids, (e.g., cinchophyllamines, quinamine, and 3-epiquinamine) as compared to samples of C. ledgeriana from Guatemala, where quinoline alkaloids 1–4 predominate [29]. Up to 1% of the total alkaloids are found in leaves, with younger leaves having a higher concentration [26]. There are various different varieties of bark: red (Cinchona succirubra), grey (C. micrantha and C. nitida), yellow (C. calisaya), Colombian (C. lancifolia), or colourless (C. ofcinalis), each of which has a constant ratio of alkaloids. Compared to trees with red or grey bark, which have the lower compound content, plants with yellow bark appear to have more quinine concentration [30]. Alkaloids make up 5–7% of the “red” bark of

C. succirubra, 4–7% of the bark of C. calisaya, and up to 5–14% of the bark of C. ofcinalis [29].

S. Aslam etal.

10.12 Other Chemical Constituents ofGenus Cinchona

The ndings of the phytochemical screening revealed that the tissues of Cinchona leaves and bark contain a variety of avonoids, terpenoids, tannins, saponins, and lipophilic chemicals, with varying degrees of colour intensity that may indicate their quantity of accumulation [26, 31, 32]. Thin layer chromatography (TLC) examination of Cinchona pubescens demonstrated the presence of four avonoids, catechin(23), kaempferol(24), apigenin(25), and quercetin(26) [31, 33]. Extracts of different cinchona species contain variable levels of these compounds. For instance, a leaf of C. ledgeriana extracted with 70% ethanol included avonoids, tannins, saponins, other than alkaloids, and terpenoids. The concentration of total phenol (40.23%) and avonoids (65.34%) was highest in the ethyl acetate fraction [26]. The C. succirubra extract contains the alkaloids, avonoids, amino acids, glycosides, saponins, tannins (3–10%), phenolic organic acids, terpenoids and steroids [24]. In the bark of C. calisaya, alkaloids (6.0%), avonoids (5.0%), saponins (2.0%), and cardiac glycosides (3.54%) all seemed to be found [34]. The anthroquinones are a different class of compounds present in C. pubescens. Another signicant category is essential oils, which account for 0.02 to 0.08% of all substances. Some other components have been identied including glycosides, organic acids (quinotanic acid, cinconic red), monoglycosides such as quinovic acid (3β-hydroxyurea-droxibenzoico acid), [33] Coumarins and terpene compounds [35]. Typically, Cinchona plants produce all these metabolites for protection and adaptation [31] (Fig.10.4).

10 Cinchona

https://t.me/medicina_free

231

OHO

Fig. 10.4 Important avonoids in Cinchona plant

10.13 Origin andUses ofCinchona

For decades, the bark of various cinchona species has provided the febrifuge chemical quinine, which is useful against malaria. The crust of wild cinchona trees has been intensively collected in the Andes, resulting in dwindling inhabitants. Numerous varieties as well as hybrids have been grown in warm, moist climates across the world, notably in India and Southeast Asia.

Cinchona is used to stimulate hunger, promote the ow of digestive uids, and alleviate bloating, fullness, and other stomach issues. Hemorrhoids, varicose veins, and leg cramps are among the conditions for which it is prescribed. Cinchona is used to treat moderate inuenza, swine u, the common cold, malaria, and fever in some persons. Cancer, tongue and throat illnesses, an enlarged spleen, and muscular cramps are among the other applications. Cinchona is used to dull discomfort, destroy germs, and act as an astringent in eye treatments. Cinchona extract is also used topically for haemorrhoids, ulcers, hair growth stimulation, and varicose vein management. Cinchona is used in tonic water and alcoholic drinks due to its bitter avour.

10.14 Medicinal Uses ofCinchona

Plants have long been used to cure sickness in tropical areas, and their usage has been documented since the time when individuals from the old world rst met the indigenous inhabitants of the Americas [36]. In South America, the Rubiaceae plants recognized as quina/cinchona (Cinchona spp.) and ipeca or ipecacuanha

232

https://t.me/medicina_free

(Carapichea ipecacuanha (Brot.) have sparked researcher’s attention [37]. These plant species have been utilised by numerous groups of humans throughout history, including locals and settlers [38]. Indians from South America used cinchona bark as an anti-fever remedy before it was brought to Europe around 1640. The bark controlled malaria treatment in Europe until 1820, when pure quinine was discovered and largely substituted the natural substance [3]. Cinchona bark has a bitter avour, was used to make beverages. Bitters have also been used as tonics and medications for recurring fevers; in the early 1800s, the impact of cinchona bark on fever therapy and prevention was demonstrated.

Cinchona bark was added as an adulterant to Jesuit’s bark or Peruvian bark, which was originally thought to be connected to another fever remedy called Myroxylon peruiferum. Cinchona bark may be obtained in a variety of methods. The tree could be chopped down, however, girdling is as harmful and unsustainable as the chopping of the tree, so little pieces were cut and different treatments including “mossing,” which involves applying bog to the damaged places, were utilized to let the tree to recuperate. Coppicing and cutting of side branches, which were later peeled of bark, were two other methods. Before 1820, the bark of the cinchona tree was dried, ground into ne particles, and then blended with a liquid (often wine) before being ingested. In 1820, French chemists extracted quinine from the bark before pure quinine eventually replaced the bark as the standard treatment for malarial illness. Quinine and other cinchona alkaloids, such as cinchonine, cinchonidine, and quinidine, are all antimalarial agents [39, 40]. Economically, Cinchona is the sole viable origin of quinine, and prescribed as the medicine to treat falciparum malaria [41].

S. Aslam etal.

10.15 Cinchona Alkaloids

Cinchona bark has historically been prized for its medicinal properties due to the presence of quinine and other alkaloids. For years, quinine and other cinchona alkaloids have been used as anti-pyretic and as treatments for malaria [71]. Besides these, cinchona alkaloids have various applications in the treatment of cardiac, muscular,cancer and other diseases [4].

10.16 Medicinal Uses ofQuinine andIts Derivatives

It is the primary alkaloid found in bark of the cinchona plant, which is mostly derived from Cinchona calisaya Wedd. and Cinchona pubescens Vahl. for the treatment of malaria [42]. It is the most signicant alkaloid that utilized in the form of salts, sulfate, bisulfate, hydrochloride and dichloride [26]. The rst component discovered in the bark of the Cinchona tree (Cinchona ofcinalis) that effectively reduced some malarial fevers was quinine alkaloid [72]. It can be considered the

10 Cinchona

https://t.me/medicina_free

233

rst, unpolluted, and truly dynamic chemotherapeutic in this context. Regardless of the fact that quinine has a limited therapeutic window and the malaria vector Plasmodium falciparum is becoming increasingly resistant to it, it may still compete with newer antimalarial medicines, making it an essential medication for severe malaria infections [4]. The small half-life, unpleasant taste, as well as severe adverse health impacts such as headache, giddiness, seasickness, vomiting, and hemolysis all contributed to quinine’s long-term usage as an antimalarial drug. Furthermore, drug resistance hindered the effectiveness of malarial infection remedy [43]. Numerous new antimalarial medicines using quinine scaffolds, such as hydroxyethylapoquinine, have been developed recently to decrease disadvantages as well as avoid drug resistance [44, 45].

Quinine is one of the most effective antimalarial alkaloids among the cinchona alkaloids [46]. Phenobarbital has the ability to partially overcome quinine resistance, according to a modest in vitro research [47]. It is being investigated whether calcium antagonists and additional medications (such prochlorperazine) can assist P. falciparum to restore its quinine resistance [48]. Antibiotics (such as artemisinin, artemether, clindamycin, doxycycline, and meoquine) are being studied and utilised in conjunction with quinine to treat resistant P. falciparum strains [49, 50]. Quinine is supposed to have an antipyretic effect. Despite the fact that quinine given before acetaminophen causes a faster reduction in temperature as compared to quinine given after acetaminophen, quinine has no impact on temperature [51]. Quinine suppresses cancer cell growth by inuencing apoptosis and inhibiting cell proliferation in a dosage and time dependent manner [52]. Anticancer medications such as bleomycin, cisplatin, anthracyclines, and radiation have been shown to cause an increase in the production of intracellular ROS [2].

In the nineteenth century, quinine was recognised as an ototoxic medication. Quinine was employed as an analgesic (for herpes zoster, otalgia) and as a healing mediator (for vertigo, Menière’s illness, furuncles in the auditory canal, and purulent otitis media) in a variety of otologic conditions [53].

Maternal anaemia, delay in intrauterine development, low weight, premature births, and abortion are all complications of malarial infection during pregnancy. In order to minimise the above-mentioned negative consequences, it is vital to prevent and treat malaria during pregnancy. Because the use of artemisinin compounds during this period has not been proved due to its safety issues, the WHO now advises the pregnant women to use quinine with clindamycin for curing malarial infection in their rst week to week 12 pregnancy (WHO 2010). Because most medical studies exclude women in their rst 12weeks, evidence on the efciency as well as protection of anti-malarial medications in this time period of pregnancy is scarce. The majority of the evidence regarding quinine’s safety in pregnancy is historical, and just a few medical studies have been available [54, 55].

For expectant women with malarial disease caused by chloroquine-resistant P. falciparum infection, quinine sulphate and clindamycin in a combined form is suggested. QS, in combination with other compounds such as clindamycin, doxycycline, or tetracycline, is a second therapy option for Plasmodium falciparum

<<< < Предыдущая 12 13 14 15 16 17 18 19 20 21 22 2324 / 5024 25 26 27 28 29 30 31 32 33 34 35 36 > Следующая >>>

Соседние файлы в папке Библиотека им академика М.И. Перельмана

#
30.08.202670 Мб0Книга_5322_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_5323_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202655 Мб0Книга_5324_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202653 Мб0Книга_5325_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202652 Мб0Книга_5326_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202652 Мб0Книга_5327_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202650 Мб0Книга_5328_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_5329_Библиотеки_им_академика_М_И_Перельмана.pdf
#
29.08.202687 Мб0Книга_533_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_5330_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202646 Мб0Книга_5333_Библиотеки_им_академика_М_И_Перельмана.pdf